Document Type

Article

Publication Date

1-15-2024

Department

Department of Mechanical Engineering-Engineering Mechanics; Department of Biomedical Engineering; Institute of Computing and Cybersystems

Abstract

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has stronger contribution than Arp2/3. Interestingly, we report a four-fold reduction in traction of cells when both Arp2/3 and myosin were inhibited, compared to cells with only myosin inhibition, while there was only a slight reduction in F-actin flow speed in those cells. We show that the conventional rigid-actin-based clutch model is insufficient to explain this force-flow behavior and requires the inclusion of F-actin’s own elasticity into consideration. Our model prediction suggests that Arp2/3 and formin modulate stiffness sensing via stiffening F-actin network with stronger effect from formin. Analysis of F-actin flow reveals stiffness-dependent fluctuation frequency in the flow speed, which is predictable only via the model considering actin elasticity. Our data and model provide a potential role of the polymerizing actin and its elasticity in myosin-independent mechanosensing.

Publisher's Statement

This is a preprint; it has not been peer reviewed by a journal.

Version of Record: A version of this preprint was published at Communications Materials on January 15th, 2024. See the published version at https://doi.org/10.21203/rs.3.rs-2679496/v1

Publication Title

Research Square

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Version

Preprint

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