Application of piconewton forces to individual filopodia reveals mechanosensory role of L-type Ca2+ channels

Artem K. Efremov, Mingxi Yao, Yuze Sun, Yee Han Tee, Michael P. Sheetz, Alexander D. Bershadsky, Boris Martinac, Jie Yan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Filopodia are ubiquitous membrane projections that play crucial role in guiding cell migration on rigid substrates and through extracellular matrix by utilizing yet unknown mechanosensing molecular pathways. As recent studies show that Ca2+ channels localized to filopodia play an important role in regulation of their formation and since some Ca2+ channels are known to be mechanosensitive, force-dependent activity of filopodial Ca2+ channels might be linked to filopodia's mechanosensing function. We tested this hypothesis by monitoring changes in the intra-filopodial Ca2+ level in response to application of stretching force to individual filopodia of several cell types using optical tweezers. Results show that stretching forces of tens of pN strongly promote Ca2+ influx into filopodia, causing persistent Ca2+ oscillations that last for minutes even after the force is released. Several known mechanosensitive Ca2+ channels, such as Piezo 1, Piezo 2 and TRPV4, were found to be dispensable for the observed force-dependent Ca2+ influx, while L-type Ca2+ channels appear to be a key player in the discovered phenomenon. As previous studies have shown that intra-filopodial transient Ca2+ signals play an important role in guidance of cell migration, our results suggest that the force-dependent activation of L-type Ca2+ channels may contribute to this process. Overall, our study reveals an intricate interplay between mechanical forces and Ca2+ signaling in filopodia, providing novel mechanistic insights for the force-dependent filopodia functions in guidance of cell migration.

Original languageEnglish (US)
Article number121477
JournalBiomaterials
Volume284
DOIs
StatePublished - May 2022

Keywords

  • Calcium signaling
  • Filopodia
  • L-type calcium channels
  • Mechanosensing
  • Optical tweezers

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Application of piconewton forces to individual filopodia reveals mechanosensory role of L-type Ca2+ channels'. Together they form a unique fingerprint.

Cite this