Application of piconewton forces to individual filopodia reveals mechanosensory role of L-type Ca2+ channels
Open accessPublished version of a preprint
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 Ca 2+ channels localized to filopodia play an important role in regulation of their formation and since some Ca 2+ channels are known to be mechanosensitive, force-dependent activity of filopodial Ca 2+ channels might be linked to filopodia's mechanosensing function. We tested this hypothesis by monitoring changes in the intra-filopodial Ca 2+ 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 Ca 2+ influx into filopodia, causing persistent Ca 2+ oscillations that last for minutes even after the force is released. Several known mechanosensitive Ca 2+ channels, such as Piezo 1, Piezo 2 and TRPV4, were found to be dispensable for the observed force-dependent Ca 2+ influx, while L-type Ca 2+ channels appear to be a key player in the discovered phenomenon. As previous studies have shown that intra-filopodial transient Ca 2+ signals play an important role in guidance of cell migration, our results suggest that the force-dependent activation of L-type Ca 2+ channels may contribute to this process. Overall, our study reveals an intricate interplay between mechanical forces and Ca 2+ signaling in filopodia, providing novel mechanistic insights for the force-dependent filopodia functions in guidance of cell migration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Simple reductionist models have been useful for high resolution mechanistic understanding of tissue morphogenetic events such as defects.
“Simple reductionist models have been useful for high resolution mechanistic understanding of tissue morphogenetic events such as defects29,240,249.”
From Organoids (2022) · cites this paper as [240]
The Introduction (p. 3) and the section on mechanical stretching (p. 5) describe an experiment on individual filopodia that yields mechanistic insight into force-dependent cell-migration guidance. The Introduction (p. 2) links cell migration to tissue morphogenesis, but the paper does not study morphogenetic defects or show mechanistic understanding of a tissue-level event. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 77 · Cited by 38
Research works printed but not linked: 2
- [16]16. Schirenbeck A, Arasada R, Bretschneider T, Schleicher M, & Faix J (2005) 693 Proc. Natl. Acad. Sci. USA
- [27]27. Miihkinen M , et al. (2020) Myosin-X is required for integrin activation at filopodia - tips. bioRxiv :https://doi.org/10.1101/2020.1105.1105.078733. 719 · DOI
- Authors
- Efremov, A. K., Yao, M., Sun, Y., Tee, Y. H., Sheetz, M. P., Bershadsky, A. D., Martinac, B., & Yan, J.
- Affiliations
- National University of Singapore (SG)
- Victor Chang Cardiac Research Institute (AU)
- Corresponding author
- Efremov, Artem K.
- Yan, Jie
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 284
- Pages
- 121477
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W4220735160
- Cited by
- 38
- References
- 77
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 15 · 2023: 8 · 2022: 6 · 2021: 1 · 2020: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Biomaterials (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Medical Research Council (OFYIRG18may-0041)
- National Research Foundation Singapore (NRF-NRFI2016-03)
- Turun Yliopisto
- Agency for Science, Technology and Research
- Ministry of Health -Singapore
- Ministry of Education - Singapore (MOE2016-T3-1-002, MOE2018-T2-2-138)
- Kementerian Pendidikan Malaysia
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- filopodia, L-type calcium channels, mechanosensing, calcium oscillations, cell migration guidance, piconewton forces, optical tweezers, Piezo1, TRPV4, mechanosensitive ion channels, calcium signaling
- MeSH terms
- Calcium, Cell Movement, Extracellular Matrix, Pseudopodia, Signal Transduction, Optical Tweezers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
