Cellular Contact Guidance Emerges from Gap Avoidance

A.B.C. (Gitta) Buskermolen, Tommaso Ristori, Dylan Mostert, Mark C. van Turnhout, Siamak S. Shishvan, Sandra Loerakker, Nicholas A. Kurniawan (Corresponding author), V.S. Deshpande, Carlijn V.C. Bouten (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Scopus)

Abstract

In the presence of anisotropic biochemical or topographical patterns, cells tend to align in the direction of these cues—a widely reported phenomenon known as ‘‘contact guidance.’’ To investigate the origins of contact guidance, here, we created substrates micropatterned with parallel lines of fibronectin with dimensions spanning multiple orders of magnitude. Quantitative morphometric analysis of our experimental data reveals two regimes of contact guidance governed by the length scale of the cues that cannot be explained by enforced alignment of focal adhesions. Adopting computational simulations of cell remodeling on inhomogeneous substrates based on a statistical mechanics framework for living cells, we show that contact guidance emerges from anisotropic cell shape fluctuation and ‘‘gap avoidance,’’ i.e., the energetic penalty of cell adhesions on non-adhesive gaps. Our findings therefore point to general biophysical mechanisms underlying cellular contact guidance, without the necessity of invoking specific molecular pathways.
Original languageEnglish
Article number100055
JournalCell Reports. Physical Science
Volume1
Issue number5
DOIs
Publication statusPublished - 20 May 2020

Funding

The authors thank Prof. M.-J. Goumans for kindly sharing CMPC cell line. This work has been supported by the Impuls Program of the Eindhoven University of Technology ; the Netherlands Cardio Vascular Research Initiative : The Dutch Heart Foundation , Dutch Federation of University Medical Centers , the Netherlands Organization for Health Research , and Development and the Royal Netherlands Academy of Sciences (“CVON 1Valve”); the Ministry of Education, Culture and Science for the Gravitation Program 024.003.103 “Materials Driven Regeneration”; and the European Research Council (grant 851960 ; N.A.K.).

FundersFunder number
Dutch Federation of University Medical Centers
Royal Netherlands Academy of Sciences
Horizon 2020 Framework Programme851960
European Research Council
ZonMw : Dutch Organisation for Health Research and Development
Hartstichting
Eindhoven University of Technology
Ministerie van Onderwijs, Cultuur en Wetenschap

    Keywords

    • cell adhesion
    • cell alignment
    • cell organization
    • contact guidance
    • focal adhesion
    • microcontact printing
    • protein patterning
    • statistical mechanics
    • stress fibers
    • substrate anisotropy

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