Cell-intrinsic adaptation of lipid composition to local crowding drives social behaviour

Nature. 2015 Jul 2;523(7558):88-91. doi: 10.1038/nature14429. Epub 2015 May 25.

Abstract

Cells sense the context in which they grow to adapt their phenotype and allow multicellular patterning by mechanisms of autocrine and paracrine signalling. However, patterns also form in cell populations exposed to the same signalling molecules and substratum, which often correlate with specific features of the population context of single cells, such as local cell crowding. Here we reveal a cell-intrinsic molecular mechanism that allows multicellular patterning without requiring specific communication between cells. It acts by sensing the local crowding of a single cell through its ability to spread and activate focal adhesion kinase (FAK, also known as PTK2), resulting in adaptation of genes controlling membrane homeostasis. In cells experiencing low crowding, FAK suppresses transcription of the ABC transporter A1 (ABCA1) by inhibiting FOXO3 and TAL1. Agent-based computational modelling and experimental confirmation identified membrane-based signalling and feedback control as crucial for the emergence of population patterns of ABCA1 expression, which adapts membrane lipid composition to cell crowding and affects multiple signalling activities, including the suppression of ABCA1 expression itself. The simple design of this cell-intrinsic system and its broad impact on the signalling state of mammalian single cells suggests a fundamental role for a tunable membrane lipid composition in collective cell behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • Adaptation, Physiological*
  • Animals
  • Cell Communication / physiology*
  • Cell Count
  • Cell Line, Tumor
  • Cell Membrane / chemistry*
  • Fibroblasts / chemistry
  • Fibroblasts / cytology*
  • Fibroblasts / enzymology
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lipids / chemistry*
  • Mice
  • Models, Biological
  • Signal Transduction*
  • Transcriptome

Substances

  • ATP Binding Cassette Transporter 1
  • Forkhead Transcription Factors
  • Intracellular Signaling Peptides and Proteins
  • Lipids
  • Focal Adhesion Protein-Tyrosine Kinases

Associated data

  • GEO/GSE43873