bims-ecemfi 2025-02-23 papers

bioRxiv. 2025 Feb 06. pii: 2025.01.31.635980. [Epub ahead of print]

Swirling motion of breast cancer cells radially aligns collagen fibers to enable collective invasion.

Aashrith Saraswathibhatla, Md Foysal Rabbi, Sushama Varma, Vasudha Srivastava, Olga Ilina, Naomi Hassan Kahtan Alyafei, Louis Hodgson, Zev Gartner, Peter Friedl, Robert West, Taeyoon Kim, Ovijit Chaudhuri.

In breast cancer (BC), radial alignment of collagen fibers at the tumor-matrix interface facilitates collective invasion of cancer cells into the surrounding stromal matrix, a critical step toward metastasis. Collagen remodeling is driven by proteases and cellular forces, mediated by matrix mechanical plasticity, or irreversible matrix deformation in response to force. However, the specific mechanisms causing collagen radial alignment remain unclear. Here, we study collective invasion of BC tumor spheroids in collagen-rich matrices. Increasing plasticity to BC-relevant ranges facilitates invasion, with increasing stiffness potentiating a transition from single cell to collective invasion. At enhanced plasticity, cells radially align collagen at the tumor-matrix interface prior to invasion. Surprisingly, cells migrate tangentially to the tumor-matrix interface in a swirling-like motion, perpendicular to the direction of alignment. Mechanistically, swirling generates local shear stresses, leading to distally propagating contractile radial stresses due to negative normal stress, an underappreciated property of collagen-rich matrices. These contractile stresses align collagen fibers radially, facilitating collective invasion. The basement membrane (BM), which separates epithelia from stroma in healthy tissues, acts as a mechanical insulator by preventing swirling cells from aligning collagen. Thus, after breaching the BM, swirling of BC cells at the tumor-stroma interface radially aligns collagen to facilitate invasion.

DOI: https://doi.org/10.1101/2025.01.31.635980

Biomater Sci. 2025 Feb 17.

Matrix deformation and mechanotransduction as markers of breast cancer cell phenotype alteration at matrix interfaces.

Cornelia Clemens, Rosa Gehring, Philipp Riedl, Tilo Pompe.

The dissemination of metastatic cells from the primary tumor into the surrounding tissue is a key event in the progression of cancer. This process involves the migration of cells across defined tissue interfaces that separate the dense tumor tissue from the adjacent healthy tissue. Prior research showed that cell transmigration across collagen I matrix interfaces induces a switch towards a more aggressive phenotype including a change in directionality of migration and chemosensitivity correlated to increased DNA damage during transmigration. Hence, mechanical forces acting at the nucleus during transmigration are hypothesized to trigger phenotype switching. Here, we present results from a particle image velocimetry (PIV) based live cell analysis of breast cancer cell transmigration across sharp matrix interfaces constituted of two collagen type I networks with different pore sizes. We found strong and highly localized collagen network deformation caused by cellular forces at the moment of crossing interfaces from dense into open matrices. Additionally, an increased contractility of transmigrated cells was determined for cells with the switch phenotype. Moreover, studies on mechanotransductive signaling at the nucleus, emerin translocation and YAP activation, indicated a misregulation of these signals for transmigrated cells with altered phenotype. These findings show that matrix interfaces between networks of different pore sizes mechanically challenge invasive breast cancer cells during transmigration by a strong asymmetry of contracting forces, impeding nuclear mechanotransduction pathways, with a subsequent trigger of more aggressive phenotypes.

DOI: https://doi.org/10.1039/d4bm01589d

Soft Matter. 2025 Feb 20.

Poroelasticity and permeability of fibrous polymer networks under compression.

Paul Mollenkopf, Jakub A Kochanowski, Yifei Ren, Kyle H Vining, Paul A Janmey, Prashant K Purohit.

Soft biopolymer networks play pivotal roles in governing cellular mechanics, tissue structure, and physiological processes such as blood coagulation. Understanding their permeability and mechanical responses under compression is crucial for elucidating mass transport phenomena and their impact on extra- and intra-cellular behavior as well as processes affecting functionality of blood clots, cartilage and other fibrous tissues. The nonlinear responses of these networks to mechanical stresses prevent application of established linear poro-elasticity models. Despite extensive studies of fibrous network viscoelastic properties under shear deformations, their dynamic responses to compressive deformations remain poorly understood, particularly in physiological contexts of growth and collective migration of solid bodies. Conventional experimental techniques face challenges in accurately evaluating the permeability of these networks, hindering comprehensive understanding of their poromechanical behavior. In this study, we employ a novel poroelastic hybrid approach combining rheometer-based compression rheology with camera-facilitated sample shape detection to directly measure fluid flux and network permeability under controlled compressive strains. Accompanying experimental investigations, a continuum model implemented in finite elements, and an analytical model are developed to interpret the findings. The experimental data align well with the analytical model, revealing the emergence and disappearance of distinct densification regimes within the gel under mechanical stress. This study advances our understanding of the intricate interplay between mechanical forces, fluid flow, and structural properties in soft biopolymer networks, with a specific focus on fibrin- and collagen-based gels which represent the most abundant protein networks in the extracellular environment.

DOI: https://doi.org/10.1039/d4sm01223b

Dev Cell. 2025 Feb 07. pii: S1534-5807(25)00036-X. [Epub ahead of print]

Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages.

Xinyi Huang, Zhifang Li, Yuhan Huang, Qian Zhang, Yanqin Cui, Xuemeng Shi, Yaming Jiu.

Macrophages possess the capacity to degrade extracellular matrix (ECM), but the specific roles of different cytoskeletal structures in controlling this process are incompletely understood. Here, we report that the inward flow of actin stress fibers delivers endocytosed ECM for lysosomal elimination, replenishing the pool of enzymes for extracellular ECM hydrolysis in actin-rich podosomes. Vimentin deficiency disrupted the balance between stress fibers and podosomes, impairing ECM degradation through integrin CD11b in THP-1 macrophages. In lung adenocarcinoma patient samples, M2-type macrophages exhibit a tighter podosome organization, surrounded by compact vimentin filaments, than M1-type. In vitro experiments verified that the invasion ability of A549 lung carcinoma cells was enhanced when accompanied by wild type, but not vimentin knockout M2-type THP-1, macrophages. Subcutaneous injections of macrophages and tumor cells in nude mice showed that vimentin in macrophages can reduce tumor collagen fibers. Together, our findings provide insights into the cytoskeletal dynamics governing macrophage ECM degradation.

Keywords: CD11b; ECM degradation; actin filaments; cancer invasion; intermediate filaments; lung adenocarcinoma; macrophage; podosome; stress fibers; vimentin

DOI: https://doi.org/10.1016/j.devcel.2025.01.016