bims-ecemfi 2026-08-09 papers

ACS Appl Mater Interfaces. 2026 Aug 05. 18(30): 40536-40553

Model-Assisted Prioritization of Gelatin Methacryloyl (GelMA) Hydrogel Formulations for Three-Dimensional Cell Culture.

Peisong Yin, Xin Wang, Suqing Liu, Yujun Huang, Meiyi Huang, Yu Zhang, Ruijun Peng, Jingwen Sun, Yaobin Wu, Ling Wang.

Owing to highly tunable mechanics, gelatin methacryloyl (GelMA) hydrogels are widely exploited for three-dimensional (3D) cell culture, whereas limited experimental sampling restricts efficient formulation screening. In this work, we developed a BNN-based modeling pipeline to map GelMA hydrogels with various cross-linking parameters toward linear viscoelastic moduli and nonlinear critical stress, thereby categorizing all tested formulations into low/intermediate/high stable mechanical windows. Calibration on C2C12 myoblast morphologies confirmed that nonlinear critical stress complements linear rheological parameters to refine the screening priority of cell-compatible hydrogel recipes. Subsequent validation with primary cardiomyocytes demonstrated consistent morphological trends matching the predefined mechanical windows, alongside ambiguous boundary formulations. Our findings construct a bounded prioritization strategy to rapidly select GelMA compositions under sparse experimental conditions, with further prospective validations demanded before generalized predictive use for diverse tissue engineering scenarios.

Keywords: Gelatin methacryloyl (GelMA); Hydrogels; Mechanical windows; Rheology; Three-dimensional cell culture

DOI: https://doi.org/10.1021/acsami.6c11606

Mol Biol Cell. 2026 Aug 05. mbcE26010052

Vimentin bridges scales to convert polarized cell locomotion into coordinated collective migration.

Sudheer Kumar Peneti, Satish Babu Morparthi, Clémence Thiant, Joseph d' Alessandro, Lucas Anger, Ranjith Chilupuri, Tien Dang, Manon Arnaud, Julia Eckert, Stéphane Vassilopoulos, Benoit Ladoux, René-Marc Mège.

Collective cell migration is central in development and disease. Vimentin is an intermediate filament protein expressed by epithelial cells at the edge of wounds where collective cell migration is most efficient. Yet, its functional role in this context remains underexplored. Here, we show that vimentin, over-expressed in cells undergoing partial epithelial to mesenchymal transition at the edge of epithelial monolayers, has a multiscale impact on the whole monolayer mechano-dynamics. Vimentin knock-down delays wound closure, reduces cell coordination, while increasing traction forces exerted by cells on the substratum. It also disrupts the directionality of leader cells migration, as well as the cohesion and coordinated motion of cells deep in the monolayer. We further show that vimentin promotes the conversion of polarized cell locomotion into coordinate collective migration by polarizing actin, focal adhesions and traction forces, sustaining leader cell's lamellipodium protrusive activity and directionality, while allowing mechanical coupling of leader with follower cells. Altogether, we show that vimentin is essential for bridging polarized single cell locomotion and coordinated collective migration to allow efficient collective migration. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

DOI: https://doi.org/10.1091/mbc.E26-01-0052

Sci Adv. 2026 Aug 07. 12(32): eaed5802

SCHEPHERD: A modular, programmable, direct current platform to control cell behavior.

Yubin Lin, Jeremy S Yodh, Celeste Rodriguez, Paul Kreymborg, Daniel J Cohen.

Spanning frogs, fish, and humans, direct current (dc) bioelectric cues play critical roles beyond neuromuscular function, such as modulating morphogenesis, immune response, and healing through electrotaxis-electrically directed cell migration. Harnessing this potential requires dedicated, versatile tools. However, standardized, accessible, and reproducible infrastructure capable of dc stimulation remains a challenge. We present SCHEPHERD: a universal, electrobioreactor integrating eight stimulation channels and modular inserts to enable most electrotaxis assays in one device (cells, monolayers, and 3D spheroids) while enabling powerful, expanded capabilities. SCHEPHERD revealed through parameter sweeps that dc fields act like a "steering wheel and gas pedal" for cell migration. We then used live confocal imaging to observe electrically reprogrammed F-actin dynamics. Last, our multipolar inserts generated complex spatial electrical patterns that reorganize engineered tissue dynamics. By substantially improving accessibility through modularity and an open-source, graphically programmed, stand-alone stimulator, we hope that SCHEPHERD can help broaden the community studying these important dc bioelectric phenomena.

DOI: https://doi.org/10.1126/sciadv.aed5802

Macromol Rapid Commun. 2026 Aug 02. e70386

Coupled Environmental Effects in Competitive Inhibition of Dynamic Hydrazone Hydrogels.

Sirilak Mekcham, Alexander D Claiborne, Megan S Rothenberg, Owen A Lee, Elizabeth Thompson, Megan R Hill.

Dynamic benzyl-hydrazone crosslinks are widely used in covalent adaptable hydrogels due to their hydrolytic stability and tunable exchange kinetics. This reversibility enables competitive inhibition strategies in which small-molecule competitors modulate network dynamics by replacing crosslinking sites. Here, we demonstrate that adding molecules to compete with crosslinks can unintentionally perturb hydrogel mechanics through environmental effects, including changes in pH and ion concentration, in addition to direct bond disruption. In benzyl-hydrazone hydrogels, methyl hydrazine competitors unexpectedly increased the average relaxation time rather than accelerating network exchange. To decouple environmental effects from competitive inhibition, we systematically investigate how pH, ion concentration, and buffer composition influence hydrogel mechanics. We find that increasing ion concentration enhances the storage modulus, consistent with salt-mediated stabilization. Comparison across biologically relevant media further reveals that relaxation dynamics vary significantly with buffer identity, even when elastic moduli remain similar. Notably, more basic environments lead to markedly slower network relaxation, even in the presence of competitors to the crosslink. These findings demonstrate that, in competitively inhibited benzyl-hydrazone hydrogels, pH, ion concentration, and buffer identity can influence network mechanics in ways that differ from the expected effects of competitor addition alone, highlighting the need for careful interpretation of competitive inhibition experiments.

Keywords: buffer types; competitive binder; covalent adaptable networks (CANs); hydrogels; ion concentration; pH; viscoelasticity

DOI: https://doi.org/10.1002/marc.70386

Bioact Mater. 2026 Dec;66 1026-1041

Cells perceive the distribution differences of adhesion ligands and consequently establish cellular polarization to regulate osteogenic differentiation.

Jinsheng Li, Ming Yang, Guowen Duan, Jianhao Huang, Tao Shen, Jie Cui, Keke Huang, Qiting Ge, Liming Yang, Jingyi Sheng, Jie Weng, Tailin Guo, Zhihong Xu, Jizi Liu, Ning Gu, Qing Jiang.

Engineering implant topography has emerged as a promising strategy to promote bone regeneration in complex fractures and large bone defects. Among such topographies, TiO2 nanotubes serve as a model topography and have been shown, within a certain range, to positively regulate osteogenic differentiation through diameter-dependent effects. However, the underlying mechanisms remains fragmentary. Here, we revealed how cells perceived nanotube interfaces and identified the intracellular force-based mechanotransduction that arose from interface perception. We unexpectedly found that cellular perception of nanotube interfaces depended on diameter-associated topographical cues that induced differential distribution of adhesive ligands. Cells engaged these adhesive ligands to modulate focal adhesion (FA) organization, with small and many FAs forming on the small-diameter nanotubes (30 nm), whereas fewer but larger FAs formed on the large-diameter nanotubes (100 nm). Fewer but larger FAs regulated cytoskeletal assembly, generating greater intracellular force and enhancing cellular polarization. Furthermore, large-diameter nanotubes promoted nuclear pore deformation and YAP nuclear translocation, leading to enhanced osteogenic differentiation both in vitro and in vivo. Together, our findings suggest that nanotube diameter-dependent geometry regulates the spatial presentation of adhesive ligands and subsequently influences FA maturation, cellular polarization, and YAP-associated mechanotransduction. This study provides mechanistic insight into how implant nanotopography modulates osteogenic responses and offers a theoretical basis for the rational design of osteogenic implant surfaces.

Keywords: Adhesive ligand distribution; Cellular polarization; Focal adhesion maturation; Nanotube-based topography; Osteogenic mechanotransduction

DOI: https://doi.org/10.1016/j.bioactmat.2026.07.031