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

Title: Changes in single-molecule integrin dynamics linked to local cellular behavior.
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Name(s): Jaqaman, Khuloud, author
Galbraith, James A, author
Davidson, Michael W, author
Galbraith, Catherine G, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-05-15
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_pmch_27009207 (IID), 10.1091/mbc.E16-01-0018 (DOI), PMC4865314 (PMCID), 27009207 (RID), 27009207 (EID), mbc.E16-01-0018 (PII)
Grant Number: P50 GM068762
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865314.
Subject(s): Animals
CHO Cells
Cricetulus
Diffusion
Humans
Integrins/chemistry
Integrins/genetics
Integrins/metabolism
Integrins/physiology
Macromolecular Substances
Microscopy, Fluorescence/methods
Models, Biological
Molecular Dynamics Simulation
Molecular Imaging/methods
Structure-Activity Relationship
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_27009207
Owner Institution: FSU
Is Part Of: Molecular biology of the cell.
1939-4586
Issue: iss. 10, vol. 27

Choose the citation style.
Jaqaman, K., Galbraith, J. A., Davidson, M. W., & Galbraith, C. G. (2016). Changes in single-molecule integrin dynamics linked to local cellular behavior. Molecular Biology Of The Cell. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_27009207