Abstract
Cell migration is heavily interconnected with plasma membrane protrusion and retraction (collectively termed "membrane dynamics"). This makes it difficult to distinguish regulatory mechanisms that differentially influence migration and membrane dynamics. Yet such distinctions may be valuable given evidence that cancer cell invasion in 3D may be better predicted by 2D membrane dynamics than by 2D cell migration, implying a degree of functional independence between these processes. Here, we applied multi-scale single cell imaging and a systematic statistical approach to disentangle regulatory associations underlying either migration or membrane dynamics. This revealed preferential correlations between membrane dynamics and F-actin features, contrasting with an enrichment of links between cell migration and adhesion complex properties. These correlative linkages were often non-linear and therefore context-dependent, strengthening or weakening with spontaneous heterogeneity in cell behavior. More broadly, we observed that slow moving cells tend to increase in area, while fast moving cells tend to shrink, and that the size of dynamic membrane domains is independent of cell area. Overall, we define macromolecular features preferentially associated with either cell migration or membrane dynamics, enabling more specific interrogation and targeting of these processes in future.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism*
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Actin Cytoskeleton / ultrastructure
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Actins / metabolism
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Actins / ultrastructure
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Cell Adhesion
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Cell Line, Tumor
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Cell Membrane / metabolism*
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Cell Membrane / ultrastructure
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Cell Movement
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Cell-Matrix Junctions / metabolism*
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Cell-Matrix Junctions / ultrastructure
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Epithelial Cells / metabolism*
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Epithelial Cells / ultrastructure
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Extracellular Matrix / metabolism*
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Extracellular Matrix / ultrastructure
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Gene Expression
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Genes, Reporter
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Membrane Fluidity
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Microscopy, Confocal
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Paxillin / genetics
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Paxillin / metabolism
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Plasmids / chemistry
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Plasmids / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Respiratory Mucosa / metabolism
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Respiratory Mucosa / ultrastructure
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Transfection
Substances
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Actins
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PXN protein, human
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Paxillin
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Recombinant Fusion Proteins
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enhanced green fluorescent protein
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Green Fluorescent Proteins
Grants and funding
This work was supported by grants to SS from the EU-FP7– Systems Microscopy NoE (Grant No. HEALTH-F4-2010-258068,
www.systemsmicroscopy.eu), the Center for Innovative Medicine at Karolinska Institutet (
www.ki.se), the Swedish Research Council (Grants No. 340-2012-6001 and 521-2012-3180,
www.vr.se), and the Swedish Cancer Society (
www.cancerfonden.se). Imaging was performed at the Live Cell Imaging unit/Nikon Center of Excellence, Department of Biosciences and Nutrition, Karolinska Institutet, Sweden, supported by grants from the Knut and Alice Wallenberg Foundation (
www.wallenberg.com/kaw), the Swedish Research Council, the Centre for Innovative Medicine and the Jonasson donation to the School of Technology and Health, Kungliga Tekniska Högskolan (
www.kth.se), Sweden. HSA was supported by a scholarship by the Higher Education Commission of Pakistan (
www.hec.gov.pk). JMK was supported by Magnus Bergvalls stiftelse (
www.magnbergvallsstiftelse.nu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.