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Dynamic rigidity changes enable rapid cell migration on soft substrates

Jiapeng Yang, Yu Zhang, Shuo Wang, Peng Wang, Liang Dong, Luofei Li, Yuanqi Cheng, Xiaoyu Huang, Bin Xue, Wei Wang, Chunping Jiang, Xiaosong Gu, Yi Cao, Qiang Wei

2025Nature Communications18 citationsDOIOpen Access PDF

Abstract

Cell migration is crucial in various biological processes, regulated by surrounding rigidity. Studies under static conditions suggest migration favors rigid substrates, as softer substrates (<4 kPa) do not provide sufficient traction forces. Here we show that mesenchymal stem cells (MSCs) can overcome this limitation when exposed to rapid cyclic changes in substrate rigidity. Under dynamic conditions, cell traction forces progressively rise, promoting a swift mechanical turnover of focal adhesions. This adaptation obviates the need for cell polarity and the mechanochemical turnover of focal adhesions typically required for traditional mesenchymal-type migration. The rapid migration speed together with the shape evolution during migration can be adequately predicted by our theoretical model that considers the force balance under dynamic conditions. Our findings underscore the innate capacity of cells to navigate through fluctuating mechanical cues, highlighting a versatile cellular response mechanism for understanding cell behaviors under dynamic physiological or pathological conditions.

Topics & Concepts

Cell migrationTractive forceFocal adhesionTraction (geology)Cell polarityRigidity (electromagnetism)Materials scienceMechanotransductionBiophysicsMesenchymal stem cellCellNanotechnologyMechanobiologyBiological systemComputer scienceShape changeForce dynamicsChemistryExtracellular matrixCell biologyCytoskeletonCellular Mechanics and Interactions3D Printing in Biomedical ResearchMicrofluidic and Bio-sensing Technologies