bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2024–10–20
nineteen papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Cross-Linker Architectures Impact Viscoelasticity in Dynamic Covalent Hydrogels.
  2. Substrate stiffness-dependent activation of Hippo pathway in cancer associated fibroblasts.
  3. Linking Metastatic Potential and Viscoelastic Properties of Breast Cancer Spheroids via Dynamic Compression and Relaxation in Microfluidics.
  4. Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids.
  5. Rupture Mechanics of Blood Clots: Influence of Fibrin Network Structure on the Rupture Resistance.
  6. Cardiac Matrix-Derived Granular Hydrogel Enhances Cell Function in 3D Culture.
  7. Invasion/chemotaxis- and extravasation-chip models for breast cancer bone metastasis.
  8. Inflation-induced motility for long-distance vertical migration.
  9. Heterogeneous force response of chromatin in isolated nuclei.
  10. Selective utilization of glucose metabolism guides mammalian gastrulation.
  11. Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature.
  12. A role for cross-linking proteins in actin filament network organization and force generation.
  13. A direct computational assessment of vinculin-actin unbinding kinetics reveals catch bonding behavior.
  14. A bulk-surface mechanobiochemical modelling approach for single cell migration in two-space dimensions.
  15. Physics-based prediction of moisture-capture properties of hydrogels.
  16. Cellular solids and prestressed affine networks as models of the elastic behavior of soft biological structures.
  17. YAP1 modulation of primary cilia-mediated ciliogenesis in 2D and 3D prostate cancer models.
  18. Engineering anisotropic tissue analogues: harnessing synergistic potential of extrusion-based bioprinting and extracellular matrix-based bioink.
  19. Body orientation change of neighbors leads to scale-free correlation in collective motion.
  1. Adv Healthc Mater. 2024 Oct 15. e2402059
    Cross-Linker Architectures Impact Viscoelasticity in Dynamic Covalent Hydrogels.
    Yung-Hao Lin, Junzhe Lou, Yan Xia, Ovijit Chaudhuri.
      Dynamic covalent cross-linked (DCC) hydrogels represent a significant advance in biomaterials for regenerative medicine and mechanobiology, offering viscoelasticity, and self-healing properties that more closely mimic in vivo tissue mechanics than traditional, predominantly elastic, covalent hydrogels. However, the effects of varying cross-linker architecture on DCC hydrogel viscoelasticity have not been thoroughly investigated. This study introduces hydrazone-based alginate hydrogels to explore how cross-linker architectures impact stiffness and viscoelasticity. In hydrogels with side-chain cross-linker (SCX), higher cross-linker concentrations enhance stiffness and decelerate stress relaxation, while an off-stoichiometric hydrazine-to-aldehyde ratio reduces stiffness and shortens relaxation time. In hydrogels with telechelic cross-linking, maximal stiffness and relaxation time occurs at intermediate cross-linker mixing ratio for both linear cross-linker (LX) and star cross-linker (SX), with higher cross-linker valency further enhancing these properties. Further, the ranges of stiffness and viscoelasticity accessible with the different cross-linker architectures are found to be distinct, with SCX hydrogels leading to slower stress relaxation relative to the other architectures, and SX hydrogels providing increased stiffness and slower stress relaxation versus LX hydrogels. This research underscores the pivotal role of cross-linker architecture in defining hydrogel stiffness and viscoelasticity, providing insights for designing DCC hydrogels with tailored mechanical properties for specific biomedical applications.
    Keywords:  cross‐linker architectures; dynamic covalent cross‐linking; hydrazones; hydrogels; viscoelasticity
    DOI:  https://doi.org/10.1002/adhm.202402059
  2. Biomater Adv. 2024 Oct 09. pii: S2772-9508(24)00304-2. [Epub ahead of print]166 214061
    Substrate stiffness-dependent activation of Hippo pathway in cancer associated fibroblasts.
    Gerard Rubí-Sans, Agata Nyga, Miguel A Mateos-Timoneda, Elisabeth Engel.
      The tumor microenvironment (TME) comprises a heterogenous cell population within a complex three-dimensional (3D) extracellular matrix (ECM). Stromal cells within this TME are altered by signaling cues from cancer cells to support uncontrolled tumor growth and invasion events. Moreover, the ECM also plays a fundamental role in tumor development through pathological remodeling, stiffening and interaction with TME cells. In healthy tissues, Hippo signaling pathway actively contributes to tissue growth, cell proliferation and apoptosis. However, in cancer, the Hippo signaling pathway is highly dysregulated, leading to nuclear translocation of the YAP/TAZ complex, which directly contributes to uncontrolled cell proliferation and tissue growth, and ECM remodeling and stiffening processes. Here, we compare the effect of increasing cell culture substrate stiffness, derived from tumor progression, upon the dysregulation of the Hippo signaling pathway in colorectal cancer-associated fibroblasts (CAFs) and normal colorectal fibroblasts (NFs). We correlate the dysregulation of Hippo pathway with the magnitude of the traction forces exerted by healthy and malignant stromal cells. We found that ECM stiffening is crucial in Hippo pathway dysregulation in CAFs, but not in normal fibroblasts.
    Keywords:  Cancer-associated fibroblasts; Hippo pathway; Tumor microenvironment; YAP-TAZ
    DOI:  https://doi.org/10.1016/j.bioadv.2024.214061
  3. Adv Healthc Mater. 2024 Oct 14. e2402715
    Linking Metastatic Potential and Viscoelastic Properties of Breast Cancer Spheroids via Dynamic Compression and Relaxation in Microfluidics.
    Margherita Tavasso, Ankur D Bordoloi, Elsa Tanré, Sanne A H Dekker, Valeria Garbin, Pouyan E Boukany.
      The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors and physical forces in the tumor microenvironment. Due to the lack of a comprehensive investigation of tumor tissue viscoelasticity, the relationship between such physical properties and cancer malignancy remains poorly understood. Here, the viscoelastic properties of breast cancer spheroids, 3D (in vitro) tumor models, are studied in relation to their metastatic potentials by imposing controlled, dynamic compression within a microfluidic constriction, and subsequently monitoring the relaxation of the imposed deformation. By adopting a modified Maxwell model to extract viscoelastic properties from the compression data, the benign (MCF-10A) spheroids are found to have higher bulk elastic modulus and viscosity compared to malignant spheroids (MCF-7 and MDA-MB-231). The relaxation is characterized by two timescales, captured by a double exponential fitting function, which reveals a similar fast rebound for MCF-7 and MCF-10A. Both the malignant spheroids exhibit similar long-term relaxation and display residual deformation. However, they differ significantly in morphology, particularly in intercellular movements. These differences between malignant spheroids are demonstrated to be linked to their cytoskeletal organization, by microscopic imaging of F-actin within the spheroids, together with cell-cell adhesion strength.
    Keywords:  deformation and relaxation; malignancy; microfluidics; spheroid viscoelasticity; tissue mechanics
    DOI:  https://doi.org/10.1002/adhm.202402715
  4. Cell Rep. 2024 Oct 17. pii: S2211-1247(24)01225-7. [Epub ahead of print]43(11): 114874
    Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids.
    Andrew Kjar, Mia R Haschert, José C Zepeda, A Joey Simmons, Alexis Yates, Daniel Chavarria, Melanie Fernandez, Gabriella Robertson, Adam M Abdulrahman, Hyosung Kim, Nicole T Marguerite, Rachel K Moen, Lauren E Drake, Corinne W Curry, Brian J O'Grady, Vivian Gama, Ken S Lau, Brad Grueter, Jonathan M Brunger, Ethan S Lippmann.
      Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. We determined that peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad hydrogels mapped more closely to human fetal populations and produced neurons with more spontaneous excitatory postsynaptic currents relative to Matrigel. These results provide compelling evidence that matrix-tethered signaling peptides can influence neural organoid differentiation, opening an avenue to control stem cell fate. Moreover, outcomes from this work showcase the technical utility of GelMA-Cad as a simple and defined hydrogel alternative to Matrigel for neural organoid culture.
    Keywords:  CP: Stem cell research; GelMA; Matrigel; N-cadherin; neural organoids; peptide-functionalized matrices
    DOI:  https://doi.org/10.1016/j.celrep.2024.114874
  5. Acta Biomater. 2024 Oct 10. pii: S1742-7061(24)00585-3. [Epub ahead of print]
    Rupture Mechanics of Blood Clots: Influence of Fibrin Network Structure on the Rupture Resistance.
    Ranjini K Ramanujam, Farkhad Maksudov, Rebecca A Risman, Rustem I Litvinov, John W Weisel, John L Bassani, Valeri Barsegov, Prashant K Purohit, Valerie Tutwiler.
      Embolization is a leading cause of mortality, yet we know little about clot rupture mechanics. Fibrin provides the main structural and mechanical stability to blood clots. Previous studies have shown that altering the concentration of coagulation activators (thrombin or tissue factor (TF)) has a significant impact on fibrin structure and viscoelastic properties, but their effects on rupture properties are mostly unknown. Toughness, which corresponds to the ability to resist rupture, is independent of viscoelastic properties. We used varying TF concentrations to alter the structure and toughness of human plasma clots. We performed single-edge notch rupture tests to examine fibrin toughness under a constant strain rate and we assessed viscoelastic mechanics using rheology. We utilized fluorescent confocal and scanning electron microscopy (SEM) to quantify the fibrin network structure under varying TF concentrations. Our results revealed that increased TF concentration resulted in increased number of fibrin fibers with a reduction in network pore size, thinner and shorter fibrin fibers. Increasing TF concentration yielded a maximum toughness at mid-TF concentration, such that fibrin diameter and number of fibers underlie a complex role in influencing the rupture resistance of blood clots, resulting in a nonmonotonic relationship between TF and toughness. A simple mechanical model, built on our findings from our Fluctuating Spring (FS) computational model, adopted to estimate the fracture toughness (critical energy release rate) as a function of TF predicts trends that are in good agreement with experiments. The differences in mechanical responses point to the importance of studying the structure-function relationships of fibrin networks, which may be predictive of the tendency for embolization. STATEMENT OF SIGNIFICANCE: Fibrin, a naturally occurring biomaterial, is the main mechanical and structural scaffold of blood clots that provides the necessary strength and stability to the clot, ensuring effective stemming of bleeding. The rupture of blood clots can result in the blockage of downstream vessels thereby blocking blood flow and oxygen supply. The fibrin network structure has been shown to influence the viscoelastic mechanical properties of clots, but has not been explored for fracture mechanics. Here, we modulate the fibrin network structure by varying the concentration of Tissue Factor (TF). Interestingly, the association between TF concentration and maximum toughness of the clots is non-monotonic. The variations in mechanical responses highlight the importance of studying the structure-function relationships of fibrin networks, as these may predict the tendency for embolization.
    Keywords:  Biomechanics; Fibrin; Rupture; Thrombosis; fracture
    DOI:  https://doi.org/10.1016/j.actbio.2024.10.004
  6. ACS Appl Mater Interfaces. 2024 Oct 16.
    Cardiac Matrix-Derived Granular Hydrogel Enhances Cell Function in 3D Culture.
    Rubia Shaik, Jacob Brown, Jiazhu Xu, Rabina Lamichhane, Yong Wang, Yi Hong, Ge Zhang.
      Hydrogels derived from decellularized porcine myocardial matrix have demonstrated significant potential as therapeutic delivery platforms for promoting cardiac repair after injury. Our previous study developed a fibrin-enriched cardiac matrix hydrogel to enhance its angiogenic capacities. However, the bulk hydrogel structure may limit their full potential in cell delivery. Recently, granular hydrogels have emerged as a promising class of biomaterials, offering unique features such as a highly interconnected porous structure that facilitates nutrient diffusion and enhances cell viability. Several techniques have been developed for fabricating various types of granular hydrogels, among which extrusion fragmentation is particularly appealing due to its adaptability to many types of hydrogels, low cost, and high scalability. In this study, we first confirmed the effects of the bulk cardiac matrix hydrogel on the viability of encapsulated human umbilical vein endothelial cells and human mesenchymal stem cells. We then tested the feasibility of producing granular hydrogels from both cardiac matrix and fibrin-enriched cardiac matrix through cellular cross-linking of microgels fabricated by extrusion fragmentation. Afterward, we examined the roles of the produced granular hydrogels in the embedded cells and cell spheroids. Our in vitro data demonstrate that cardiac matrix-derived granular hydrogels support optimal viability of encapsulated cells and promote sprouting of human mesenchymal stem cell spheroids. Additionally, granular hydrogel derived from fibrin-enriched cardiac matrix accelerates angiogenic sprouting of embedded human mesenchymal stem cell spheroids. The results obtained from this study lay an important foundation for the future exploration of using cardiac matrix-derived granular hydrogels for cardiac cell therapy.
    Keywords:  cardiac extracellular matrix; cell spheroids; granular hydrogel; human mesenchymal stem cells; human umbilical vein endothelial cells
    DOI:  https://doi.org/10.1021/acsami.4c12871
  7. PLoS One. 2024 ;19(10): e0309285
    Invasion/chemotaxis- and extravasation-chip models for breast cancer bone metastasis.
    Burcu Firatligil-Yildirir, Gizem Bati-Ayaz, Nonappa, Devrim Pesen-Okvur, Ozden Yalcin-Ozuysal.
      Bone is one of the most frequently targeted organs in metastatic cancers including the breast. Breast cancer bone metastasis often results in devastating outcomes as limited treatment options are currently available. Therefore, innovative methods are needed to provide earlier detection and thus better treatment and prognosis. Here, we present a new approach to model bone-like microenvironments to detect invasion and extravasation of breast cancer cells using invasion/chemotaxis (IC-) and extravasation (EX-) chips, respectively. Our results show that the behaviors of MDA-MB-231 breast cancer cells on IC- and EX-chip models correlate with their in vivo metastatic potential. Our culture model constitutes cell lines representing osteoblasts, bone marrow stromal cells, and monocytes embedded in three-dimensional (3D) collagen I-based extracellular matrices of varying composition and stiffness. We show that collagen I offers a better bone-like environment for bone cells and matrix composition and stiffness regulate the invasion of breast cancer cells. Using in situ contactless rheological measurements under cell culture conditions, we show that the presence of cells increased the stiffness values of the matrices up to 1200 Pa when monitored for five days. This suggests that the cellular composition has a significant effect on regulating matrix mechanical properties, which in turn contribute to the invasiveness. The platforms we present here enable the investigation of the underlying molecular mechanisms in breast cancer bone metastasis and provide the groundwork of developing preclinical tools for the prediction of bone metastasis risk.
    DOI:  https://doi.org/10.1371/journal.pone.0309285
  8. Curr Biol. 2024 Oct 15. pii: S0960-9822(24)01287-9. [Epub ahead of print]
    Inflation-induced motility for long-distance vertical migration.
    Adam G Larson, Rahul Chajwa, Hongquan Li, Manu Prakash.
      The vertical migrations of pelagic organisms play a crucial role in shaping marine ecosystems and influencing global biogeochemical cycles. They also form the foundation of what might be the largest daily biomass movement on Earth. Surprisingly, among this diverse group of organisms, some single-cell protists can transit depths exceeding 50 m without employing flagella or cilia. How these non-motile cells perform large migrations remains unknown. It has been previously proposed that this capability might rely on the cell's ability to regulate its internal density relative to seawater. Here, using the dinoflagellate algae Pyrocystis noctiluca as a model system, we discover a rapid cell inflation event post cell division, during which a single plankton cell expands its volume 6-fold in less than 10 min. We demonstrate this rapid cellular inflation is the primary mechanism of density control. This self-regulated cellular inflation selectively imports fluid less dense than surrounding seawater and can thus effectively sling-shot a cell and reverse sedimentation within minutes. To accommodate its dramatic cellular expansion, Pyrocystis noctiluca possesses a unique reticulated cytoplasmic architecture that enables a rapid increase in overall cell volume without diluting its cytoplasmic content. We further present a generalized mathematical framework that unifies cell-cycle-driven density regulation, stratified ecology, and associated cell behavior in the open ocean. Our study unveils an ingenious strategy employed by a non-motile plankton to evade the gravitational sedimentation trap, highlighting how precise control of cell size and cell density can enable long-distance migration in the open ocean.
    Keywords:  Stokesian sedimentation; aquaporins; biological pump; cell buoyancy; cell migration; cell size; dinoflagellate; marine ecology; osmotic regulation; plankton motility
    DOI:  https://doi.org/10.1016/j.cub.2024.09.046
  9. Cell Rep. 2024 Oct 15. pii: S2211-1247(24)01203-8. [Epub ahead of print]43(10): 114852
    Heterogeneous force response of chromatin in isolated nuclei.
    Giulia Bergamaschi, Andreas S Biebricher, Hannes Witt, Fitzroy J Byfield, Xamanie M R Seymonson, Cornelis Storm, Paul A Janmey, Gijs J L Wuite.
      A quantitative description of nuclear mechanics is crucial for understanding its role in force sensing within eukaryotic cells. Recent studies indicate that the chromatin within the nucleus cannot be treated as a homogeneous material. To elucidate its material properties, we combine optical tweezers manipulation of isolated nuclei with multi-color fluorescence imaging of lamin and chromatin to map the response of nuclei to local deformations. Force spectroscopy reveals nuclear strain stiffening and an exponential force dependence, well described by a hierarchical chain model. Simultaneously, fluorescence data show a higher compliance of chromatin compared to the nuclear envelope at strains <30%. Micrococcal nuclease (MNase) digestion of chromatin results in nuclear softening and can be captured by our model. Additionally, we observe stretching responses showing a lipid tether signature, suggesting that these tethers originate from the nuclear membrane. Our combined approach allows us to elucidate the nuclear force response while mapping the deformation of lamin, (eu)chromatin, and membrane.
    Keywords:  CP: Cell biology; CP: Molecular biology; Mechanobiology; force spectroscopy; nuclear mechanics; optical tweezers
    DOI:  https://doi.org/10.1016/j.celrep.2024.114852
  10. Nature. 2024 Oct 16.
    Selective utilization of glucose metabolism guides mammalian gastrulation.
    Dominica Cao, Jenna Bergmann, Liangwen Zhong, Anupama Hemalatha, Chaitanya Dingare, Tyler Jensen, Andy L Cox, Valentina Greco, Benjamin Steventon, Berna Sozen.
      The prevailing dogma for morphological patterning in developing organisms argues that the combined inputs of transcription factor networks and signalling morphogens alone generate spatially and temporally distinct expression patterns. However, metabolism has also emerged as a critical developmental regulator1-10, independent of its functions in energy production and growth. The mechanistic role of nutrient utilization in instructing cellular programmes to shape the in vivo developing mammalian embryo remains unknown. Here we reveal two spatially resolved, cell-type- and stage-specific waves of glucose metabolism during mammalian gastrulation by using single-cell-resolution quantitative imaging of developing mouse embryos, stem cell models and embryo-derived tissue explants. We identify that the first spatiotemporal wave of glucose metabolism occurs through the hexosamine biosynthetic pathway to drive fate acquisition in the epiblast, and the second wave uses glycolysis to guide mesoderm migration and lateral expansion. Furthermore, we demonstrate that glucose exerts its influence on these developmental processes through cellular signalling pathways, with distinct mechanisms connecting glucose with the ERK activity in each wave. Our findings underscore that-in synergy with genetic mechanisms and morphogenic gradients-compartmentalized cellular metabolism is integral in guiding cell fate and specialized functions during development. This study challenges the view of the generic and housekeeping nature of cellular metabolism, offering valuable insights into its roles in various developmental contexts.
    DOI:  https://doi.org/10.1038/s41586-024-08044-1
  11. bioRxiv. 2024 Oct 11. pii: 2024.10.08.617332. [Epub ahead of print]
    Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature.
    Rui Gong, Matthew J Reynolds, Xiaoyu Sun, Gregory M Alushin.
      The E-cadherin-β-catenin-αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical force and auxiliary binding partners converge to stabilize the cadherin-catenin complex's inherently weak binding to actin filaments (F-actin) through unclear mechanisms. Here we show that afadin's coiled-coil (CC) domain and vinculin synergistically enhance the cadherin-catenin complex's F-actin engagement. The cryo-EM structure of an E-cadherin-β-catenin-αE-catenin-vinculin-afadin-CC supra-complex bound to F-actin reveals that afadin-CC bridges adjacent αE-catenin actin-binding domains along the filament, stabilizing flexible αE-catenin segments implicated in mechanical regulation. These cooperative binding contacts promote the formation of supra-complex clusters along F-actin. Additionally, cryo-EM variability analysis links supra-complex binding along individual F-actin strands to nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates a mechanistic framework by which vinculin and afadin tune cadherin-catenin complex-cytoskeleton coupling to support AJ function across varying mechanical regimes.
    DOI:  https://doi.org/10.1101/2024.10.08.617332
  12. Proc Natl Acad Sci U S A. 2024 Oct 22. 121(43): e2407838121
    A role for cross-linking proteins in actin filament network organization and force generation.
    Jennifer M Hill, Songlin Cai, Michael D Carver, David G Drubin.
      The high turgor pressure across the plasma membrane of yeasts creates a requirement for substantial force production by actin polymerization and myosin motor activity for clathrin-mediated endocytosis (CME). Endocytic internalization is severely impeded in the absence of fimbrin, an actin filament crosslinking protein called Sac6 in budding yeast. Here, we combine live-cell imaging and mathematical modeling to gain insights into the role of actin filament crosslinking proteins in force generation. Genetic manipulation showed that CME sites with more crosslinking proteins are more effective at internalization under high load. Simulations of an experimentally constrained, agent-based mathematical model recapitulate the result that endocytic networks with more double-bound fimbrin molecules internalize the plasma membrane against elevated turgor pressure more effectively. Networks with large numbers of crosslinks also have more growing actin filament barbed ends at the plasma membrane, where the addition of new actin monomers contributes to force generation and vesicle internalization. Our results provide a richer understanding of the crucial role played by actin filament crosslinking proteins during actin network force generation, highlighting the contribution of these proteins to the self-organization of the actin filament network and force generation under increased load.
    Keywords:  actin; clathrin-mediated endocytosis; crosslinking proteins; mathematical modeling
    DOI:  https://doi.org/10.1073/pnas.2407838121
  13. bioRxiv. 2024 Oct 13. pii: 2024.10.10.617580. [Epub ahead of print]
    A direct computational assessment of vinculin-actin unbinding kinetics reveals catch bonding behavior.
    Willmor J Peña Ccoa, Fatemah Mukadum, Aubin Ramon, Guillaume Stirnemann, Glen M Hocky.
      Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular mechanotransduction. In this study, we present a comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate the thermodynamic, kinetic, and mechanistic aspects of this phenomenon at physiologically relevant forces. We dissect a catch bond mechanism in which force shifts vinculin between either a weakly- or strongly-bound state. Our results demonstrate that models for these states have unbinding times consistent with those from single-molecule studies, and suggest that both have some intrinsic catch bonding behavior. We provide atomistic insight into this behavior, and show how a directional pulling force can promote the strong or weak state. Crucially, our strategy can be extended to capture the difficult-to-capture effects of small mechanical forces on biomolecular systems in general, and those involved in mechanotransduction more specifically.
    DOI:  https://doi.org/10.1101/2024.10.10.617580
  14. J Theor Biol. 2024 Oct 15. pii: S0022-5193(24)00251-0. [Epub ahead of print] 111966
    A bulk-surface mechanobiochemical modelling approach for single cell migration in two-space dimensions.
    David Hernandez-Aristizabal, Diego-Alexander Garzon-Alvarado, Carlos-Alberto Duque-Daza, Anotida Madzvamuse.
      In this work, we present a mechanobiochemical model for two-dimensional cell migration which couples mechanical properties of the cell cytosol with biochemical processes taking place near or on the cell plasma membrane. The modelling approach is based on a recently developed mathematical formalism of evolving bulk-surface partial differential equations of reaction-diffusion type. We solve these equations using finite element methods within a moving-mesh framework derived from the weak formulation of the evolving bulk-surface PDEs. In the present work, the cell cytosol interior (bulk) dynamics are coupled to the cell membrane (surface) dynamics through non-homogeneous Dirichlet boundary conditions. The modelling approach exhibits both directed cell migration in response to chemical cues as well as spontaneous migration in the absence of such cues. As a by-product, the approach shows fundamental characteristics associated with single cell migration such as: (i) cytosolic and membrane polarisation, (ii) actin dependent protrusions, and (iii) continuous shape deformation of the cell during migration. Cell migration is an ubiquitous process in life that is mainly triggered by the dynamics of the actin cytoskeleton and therefore is driven by both mechanical and biochemical processes. It is a multistep process essential for mammalian organisms and is closely linked to a vast diversity of processes; from embryonic development to cancer invasion. Experimental, theoretical and computational studies have been key to elucidate the mechanisms underlying cell migration. On one hand, rapid advances in experimental techniques allow for detailed experimental measurements of cell migration pathways, while, on the other, computational approaches allow for the modelling, analysis and understanding of such observations. The bulk-surface mechanobiochemical modelling approach presented in this work, set premises to study single cell migration through complex non-isotropic environments in two- and three-space dimensions.
    Keywords:  ALE-moving mesh methods; Bulk-surface finite element method; Bulk-surface moving-mesh finite element method (BS-MFEM); Bulk-surface partial differential equations; Bulk-surface reaction–diffusion; Cell migration; Cell motility; Mechanobiochemical modelling; Moving-mesh method
    DOI:  https://doi.org/10.1016/j.jtbi.2024.111966
  15. Nat Commun. 2024 Oct 17. 15(1): 8948
    Physics-based prediction of moisture-capture properties of hydrogels.
    Carlos D Díaz-Marín, Lorenzo Masetti, Miles A Roper, Kezia E Hector, Yang Zhong, Zhengmao Lu, Omer R Caylan, Gustav Graeber, Jeffrey C Grossman.
      Moisture-capturing materials can enable potentially game-changing energy-water technologies such as atmospheric water production, heat storage, and passive cooling. Hydrogel composites recently emerged as outstanding moisture-capturing materials due to their low cost, high affinity for humidity, and design versatility. Despite extensive efforts to experimentally explore the large design space of hydrogels for high-performance moisture capture, there is a critical knowledge gap on our understanding behind the moisture-capture properties of these materials. This missing understanding hinders the fast development of novel hydrogels, material performance enhancements, and device-level optimization. In this work, we combine synthesis and characterization of hydrogel-salt composites to develop and validate a theoretical description that bridges this knowledge gap. Starting from a thermodynamic description of hydrogel-salt composites, we develop models that accurately capture experimentally measured moisture uptakes and sorption enthalpies. We also develop mass transport models that precisely reproduce the dynamic absorption and desorption of moisture into hydrogel-salt composites. Altogether, these results demonstrate the main variables that dominate moisture-capturing properties, showing a negligible role of the polymer in the material performance under all considered cases. Our insights guide the synthesis of next-generation humidity-capturing hydrogels and enable their system-level optimization in ways previously unattainable for critical water-energy applications.
    DOI:  https://doi.org/10.1038/s41467-024-53291-5
  16. Biomech Model Mechanobiol. 2024 Oct 15.
    Cellular solids and prestressed affine networks as models of the elastic behavior of soft biological structures.
    Dimitrije Stamenović.
      We reviewed two microstructural models, cellular solid models and prestressed affine network models, that have been used previously in studies of elastic behavior of soft biological materials. These models provide simple and mathematically transparent equations that can be used to interpret experimental data and to obtain quantitative predictions of the elastic properties of biological structures. In both models, volumetric density and elastic properties of the microstructure are key determinants of the macroscopic elastic properties. In the prestressed network model, geometrical rearrangement of the microstructure (kinematic stiffness) is also important. As examples of application of these models, we considered the shear behavior of the cytoskeleton of adherent cells, of the collagen network of articular cartilage, and of the lung parenchymal network since their ability to resist shear is important for their normal biological and physiological functions. All three networks carry a pre-existing stress (prestress). We predicted their shear moduli using the microstructural models and compared those predictions with existing experimental data. Prestressed network models of the cytoskeleton and of the lung parenchyma provided a better correspondence to experimental data than cellular solid models. Both cellular solid and prestressed network models of the cartilage collagen network provided reasonable agreements with experimental values. These findings suggested that the kinematic stiffness and material stiffness of microstructural elements were both important determinants of the shear modulus of the cytoskeleton and of the lung parenchyma, whereas elasticity of collagen fibrils had a predominant role in the cartilage shear behavior.
    Keywords:  Cellular solid; Microstructure; Modeling; Prestress; Prestressed network; Shear modulus
    DOI:  https://doi.org/10.1007/s10237-024-01894-8
  17. FEBS Lett. 2024 Oct 18.
    YAP1 modulation of primary cilia-mediated ciliogenesis in 2D and 3D prostate cancer models.
    Yingbo Guo, Mathilde Dupart, Marie Irondelle, Pascal Peraldi, Frederic Bost, Nathalie M Mazure.
      The primary cilium, a non-motile organelle present in most human cells, plays a crucial role in detecting microenvironmental changes and regulating intracellular signaling. Its dysfunction is linked to various diseases, including cancer. We explored the role of ciliated cells in prostate cancer by using Gefitinib and Jasplakinolide compounds to induce ciliated cells in both normal and tumor-like prostate cell lines. We assessed GLI1 and IFT20 expression and investigated YAP1 protein's role, which is implicated in primary cilium regulation. Finally, we examined these compounds in 3D cell models, aiming to simulate in vivo conditions. Our study highlights YAP1 as a potential target for novel genetic models to understand the primary cilium's role in mediating resistance to anticancer treatments.
    Keywords:  2D and 3D models; YAP1; hypoxia; primary cilium; prostate cancer
    DOI:  https://doi.org/10.1002/1873-3468.15029
  18. Biofabrication. 2024 Oct 15.
    Engineering anisotropic tissue analogues: harnessing synergistic potential of extrusion-based bioprinting and extracellular matrix-based bioink.
    Ashis Kumar Bera, Mohd Suhail Rizvi, Vijayasankar Kn, Falguni Pati.
      In the realm of tissue engineering, replicating the intricate alignment of cells and the extracellular matrix (ECM) found in native tissue has long been a challenge. Most recent studies have relied on complex multi-step processes to approximate native tissue alignment. To address this challenge, we introduce a novel, single-step method for constructing highly aligned fibrous structures within multi-modular three-dimensional conglomerates. Our approach harnesses the synergistic potential of extrusion-based bioprinting and the fibrillogenesis kinetics of collagen-rich decellularized ECM (dECM). We've identified three key parameters governing ECM microfiber alignment during extrusion-based bioprinting: applied shear stress, stretching or extensional force, and post-print deformation. By carefully manipulating these parameters, we've successfully created highly aligned fibrous structures within multi-modular three-dimensional conglomerates. Our technique offers an efficient solution and has been validated by computational modeling. Comprehensive analyses confirm the efficacy across various scenarios, including encapsulated, top-seeded, and migratory cells. Notably, we've demonstrated the versatility and effectiveness of our approach by bioprinting highly aligned cardiac tissue patches, which show further maturation evidenced by the expression of Troponin-T and Myo-D differentiation factor needed for contractility and myotube formation, respectively. In summary, our streamlined approach offers a robust solution for creating anisotropic tissue analogues with precise ECM organization.&#xD.
    Keywords:  Alignment; Bioprinting; Decellularized extracellular matrix; Nozzle geometry; Shear stress; Stretching
    DOI:  https://doi.org/10.1088/1758-5090/ad86ec
  19. Nat Commun. 2024 Oct 17. 15(1): 8968
    Body orientation change of neighbors leads to scale-free correlation in collective motion.
    Zhicheng Zheng, Yuan Tao, Yalun Xiang, Xiaokang Lei, Xingguang Peng.
      Collective motion, such as milling, flocking, and collective turning, is a common and captivating phenomenon in nature, which arises in a group of many self-propelled individuals using local interaction mechanisms. Recently, vision-based mechanisms, which establish the relationship between visual inputs and motion decisions, have been applied to model and better understand the emergence of collective motion. However, previous studies often characterize the visual input as a transient Boolean-like sensory stream, which makes it challenging to capture the salient movements of neighbors. This further hinders the onset of the collective response in vision-based mechanisms and increases demands on visual sensing devices in robotic swarms. An explicit and context-related visual cue serving as the sensory input for decision-making in vision-based mechanisms is still lacking. Here, we hypothesize that body orientation change (BOC) is a significant visual cue characterizing the motion salience of neighbors, facilitating the emergence of the collective response. To test our hypothesis, we reveal the significant role of BOC during collective U-turn behaviors in fish schools by reconstructing scenes from the view of individual fish. We find that an individual with the larger BOC often takes on the leading role during U-turns. To further explore this empirical finding, we build a pairwise interaction mechanism on the basis of the BOC. Then, we conduct experiments of collective spin and collective turn with a real-time physics simulator to investigate the dynamics of information transfer in BOC-based interaction and further validate its effectiveness on 50 real miniature swarm robots. The experimental results show that BOC-based interaction not only facilitates the directional information transfer within the group but also leads to scale-free correlation within the swarm. Our study highlights the practicability of interaction governed by the neighbor's body orientation change in swarm robotics and the effect of scale-free correlation in enhancing collective response.
    DOI:  https://doi.org/10.1038/s41467-024-53361-8
This page is being maintained by Thomas Krichel. It was last updated on 2025‒03‒02 at 6:13.