Chiral growth of adherent filopodia

Wenhong Li, Wen Lu Chung, Michael M. Kozlov, Ohad Medalia, Benjamin Geiger*, Alexander D. Bershadsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Adherent filopodia are elongated finger-like membrane protrusions, extending from the edges of diverse cell types and participating in cell adhesion, spreading, migration, and environmental sensing. The formation and elongation of filopodia are driven by the polymerization of parallel actin filaments, comprising the filopodia cytoskeletal core. Here, we report that adherent filopodia, formed during the spreading of cultured cells on galectin-8-coated substrates, tend to change the direction of their extension in a chiral fashion, acquiring a left-bent shape. Cryoelectron tomography examination indicated that turning of the filopodia tip to the left is accompanied by the displacement of the actin core bundle to the right of the filopodia midline. Reduction of the adhesion to galectin-8 by treatment with thiodigalactoside abolished this filopodia chirality. By modulating the expression of a variety of actin-associated filopodia proteins, we identified myosin-X and formin DAAM1 as major filopodia chirality promoting factors. Formin mDia1, actin filament elongation factor VASP, and actin filament cross-linker fascin were also shown to be involved. Thus, the simple actin cytoskeleton of filopodia, together with a small number of associated proteins are sufficient to drive a complex navigation process, manifested by the development of left-right asymmetry in these cellular protrusions.

Original languageEnglish
Pages (from-to)3704-3721
Number of pages18
JournalBiophysical Journal
Volume122
Issue number18
DOIs
StatePublished - 19 Sep 2023

Funding

FundersFunder number
ERC-SyG810057-HighResCells
Maimonides Israeli
Marie Skłodowska-Curie Network InCeM642866
Minerva Center for Aging
Molecular Genetics of Cancer
European Research Council810057
National Research Foundation
Ministry of Education - SingaporeMOE2018-T2-2-138
Ministry of Science, Technology and Space
Chinese Academy of Sciences
Ministry of Education
Israel Science Foundation3617/19 ], 2749/17
Mechanobiology Institute, SingaporeR-714-006-006-271, MOE2016-T3-1-002, MOET32021-0003

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