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Force dependence of filopodia adhesion: involvement of myosin II and formins

N.O. Alieva, A.K. Efremov, S. Hu, D. Oh, Z. Chen, M. Natarajan, H.T. Ong, A. Jégou, G. Romet-Lemonne, J.T. Groves, M.P. Sheetz, J Yan, A.D. Bershadsky
doi: https://doi.org/10.1101/195420
N.O. Alieva
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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A.K. Efremov
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
2Center for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117557, Singapore
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S. Hu
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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D. Oh
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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Z. Chen
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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M. Natarajan
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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H.T. Ong
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
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A. Jégou
3Institut Jacques Monod, 15 rue Helene Brion 75205 Paris cedex 13, France
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G. Romet-Lemonne
3Institut Jacques Monod, 15 rue Helene Brion 75205 Paris cedex 13, France
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J.T. Groves
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
4Department of Chemistry, University of California, Berkeley, CA, 94720, USA
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M.P. Sheetz
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
5Department of Biological Sciences, Columbia University, New York, New York 10027, USA
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J Yan
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
2Center for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117557, Singapore
6Department of Physics, National University of Singapore, Singapore 117542, Singapore
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A.D. Bershadsky
1Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore 117411, Singapore
7Weizmann Institute of Science, Herzl St 234, Rehovot, 7610001, Israel
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  • For correspondence: alexander.bershadsky@weizmann.ac.il
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Abstract

Filopodia are dynamic membrane protrusions driven by polymerization of an actin filament core, mediated by formin molecules at the filopodia tips. Filopodia can adhere to the extracellular matrix and experience both external and cell generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we induced sustained growth of filopodia by applying pulling force to their tips via attached fibronectin-coated beads trapped by optical tweezers. Strikingly, pharmacological inhibition or knockdown of myosin IIA, which localized to the base of filopodia, resulted in weakening of filopodia adherence strength. Inhibition of formins, which caused detachment of actin filaments from formin molecules, produced similar effect. Thus, myosin IIA-generated centripetal force transmitted to the filopodia tips through interactions between formins and actin filaments is required for filopodia adhesion. Force-dependent adhesion led to preferential attachment of filopodia to rigid versus fluid substrates, which may underlie cell orientation and polarization.

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Posted September 28, 2017.
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Force dependence of filopodia adhesion: involvement of myosin II and formins
N.O. Alieva, A.K. Efremov, S. Hu, D. Oh, Z. Chen, M. Natarajan, H.T. Ong, A. Jégou, G. Romet-Lemonne, J.T. Groves, M.P. Sheetz, J Yan, A.D. Bershadsky
bioRxiv 195420; doi: https://doi.org/10.1101/195420
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Force dependence of filopodia adhesion: involvement of myosin II and formins
N.O. Alieva, A.K. Efremov, S. Hu, D. Oh, Z. Chen, M. Natarajan, H.T. Ong, A. Jégou, G. Romet-Lemonne, J.T. Groves, M.P. Sheetz, J Yan, A.D. Bershadsky
bioRxiv 195420; doi: https://doi.org/10.1101/195420

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