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bioRxiv · 10.1101/2025.03.11.642113

Glassy Adhesion Dynamics Govern Transitions Between Sub-Diffusive and Super-Diffusive Cell Migration on Viscoelastic Substrates

Sharma, V.·Adebowale, O.·Gong, Z.·Chaudhuri, O.·Shenoy, V.
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Abstract

Cell migration is pivotal in cancer metastasis, where cells navigate the extracellular matrix (ECM) and invade distant tissues. While the ECM is viscoelastic--exhibiting time-dependent stress relaxation--its influence on cell migration remains poorly understood. Here, we employ an integrated experimental and modeling approach to investigate filopodial cancer cell migration on viscoelastic substrates and uncover a striking transition from sub-diffusive to super-diffusive behavior driven by the substrates viscous relaxation timescale. Conventional motor-clutch based migration models fail to capture these anomalous migration modes, as they overlook the complex adhesion dynamics shaped by broad distribution of adhesion lifetimes. To address this, we develop a glassy motor-clutch model that incorporates the rugged energy landscape of adhesion clusters, where multiple metastable states yield long-tailed adhesion timescales. Our model reveals that migration dynamics are governed by the interplay between cellular and substrate timescales: slow-relaxing substrates prolong trapping, leading to sub-diffusion, while fast-relaxing substrates promote larger steps limiting trapping, leading to super-diffusion. Additionally, we uncover the role of actin polymerization and contractility in modulating adhesion dynamics and driving anomalous migration. These findings establish a mechanistic framework linking substrate viscoelasticity to cell motility, with implications for metastasis and cancer progression.

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Sharma, V., Adebowale, O., Gong, Z., Chaudhuri, O., Shenoy, V.. 2025-03-14. Glassy Adhesion Dynamics Govern Transitions Between Sub-Diffusive and Super-Diffusive Cell Migration on Viscoelastic Substrates. https://doi.org/10.1101/2025.03.11.642113

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