Changes in single-molecule integrin dynamics linked to local cellular behavior

Khuloud Jaqaman, James A. Galbraith, Michael W. Davidson, Catherine G. Galbraith

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Recent advances in light microscopy permit visualization of the behavior of individual molecules within dense macromolecular ensembles in live cells. It is now conceptually possible to relate the dynamic organization of molecular machinery to cellular function. However, inherent heterogeneities, as well as disparities between spatial and temporal scales, pose substantial challenges in deriving such a relationship. New approaches are required to link discrete single-molecule behavior with continuous cellular-level processes. Here we combined intercalated molecular and cellular imaging with a computational framework to detect reproducible transient changes in the behavior of individual molecules that are linked to cellular behaviors. Applying our approach to integrin transmembrane receptors revealed a spatial density gradient underlying characteristic molecular density increases and mobility decreases, indicating the subsequent onset of local protrusive activity. Integrin mutants further revealed that these density and mobility transients are separable and depend on different binding domains within the integrin cytoplasmic tail. Our approach provides a generalizable paradigm for dissecting dynamic spatiotemporal molecular behaviors linked to local cellular events.

Original languageEnglish (US)
Pages (from-to)1561-1569
Number of pages9
JournalMolecular biology of the cell
Volume27
Issue number10
DOIs
StatePublished - May 15 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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