title: Disentangling Membrane Dynamics and Cell Migration; Differential Influences of F-actin and Cell-Matrix Adhesions.
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.
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Kowalewski
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: Hamdah
authors.initials: H
authors.lastname: Shafqat-Abbasi
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden; Division of Mathematical Statistics, Department of Mathematics, Stockholm University, Stockholm, Sweden.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Jafari-Mamaghani
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: Bereket
authors.initials: B
authors.lastname: Endrias Ganebo
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Gong
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Strömblad
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors.forename: John G
authors.initials: JG
authors.lastname: Lock
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008560:Membrane Fluidity; D018613:Microscopy, Confocal; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection
chemical_list: D000199:Actins; C496061:PXN protein, human; D051419:Paxillin; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins