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Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
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Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
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Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
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Study of Cell Migration in Microfabricated Channels
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Mechanical memory primes cells for confined migration.

Jia Wen Nicole Lee1, Yeji Chang2, Malhar S Chitnis1

  • 1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Cell Reports
|April 17, 2026
PubMed
Summary

Cells remember environmental stiffness, a phenomenon called mechanical memory, which improves their ability to migrate through confined spaces. This cellular adaptation is mediated by the NFATC2 transcription factor.

Keywords:
CP: cell biologyNFATC2cell migrationconfined migrationmechanical memorymechanotransductionsubstrate stiffnesstranscriptional regulation

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Area of Science:

  • Cell biology
  • Biophysics
  • Mechanobiology

Background:

  • Migratory cells encounter confined environments in vivo, dictated by extracellular matrix (ECM) stiffness.
  • Cells possess mechanosensitive adaptations, termed mechanical memory, influencing responses to new niches.
  • Mechanisms of mechanical memory acquisition and its impact on confined migration are poorly understood.

Purpose of the Study:

  • To investigate how mechanical memory is acquired and influences cell migration in confined spaces.
  • To screen mechanical memory across healthy and transformed cells using a combined stiffness priming and confinement platform.
  • To identify molecular mediators of mechanical memory in confined cell migration.

Main Methods:

  • Stiffness priming using polyacrylamide hydrogels.
  • Utilizing a confinement platform to assess cell migration.
  • Dose-and-passage screening approach.
  • Bulk RNA sequencing to identify key transcription factors.
  • NFATC2 inhibition to validate its role.

Main Results:

  • Cells primed on soft substrates demonstrated enhanced navigation within confined spaces.
  • NFATC2 was identified as a crucial transcription factor mediating mechanical memory via genetic reprogramming.
  • NFATC2 inhibition abrogated memory acquisition and improved confined migration.
  • Highly invasive cancer cells exhibited impaired retention of mechanically induced phenotypes.

Conclusions:

  • Mechanical memory is a cell-intrinsic mechanism regulating migration in confined environments.
  • NFATC2 plays a critical role in acquiring and expressing mechanical memory for enhanced confined migration.
  • Differential adaptation strategies exist between healthy and invasive cancer cells regarding mechanical memory.