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Coherent motions in confluent cell monolayer sheets.

ABSTRACT: Cell migration plays a pivotal role in many physiologically important processes such as embryogenesis, wound-healing, immune defense, and cancer metastasis. Although much effort has been directed toward motility of individual cells, the mechanisms underpinning collective cell migration remain poorly understood. Here we develop a collective motility model that incorporates cell mechanics and persistent random motions of individual cells to study coherent migratory motions in epithelial-like monolayers. This model, in absence of any external chemical signals, is able to explain coordinate rotational motion seen in systems ranging from two adherent cells to multicellular assemblies. We show that the competition between the active persistent force and random polarization fluctuation is responsible for the robust rotation. Passive mechanical coupling between cells is necessary but active chemical signaling between cells is not. The predicted angular motions also depend on the geometrical shape of the underlying substrate: cells exhibit collective rotation on circular substrates, but display linear back-and-forth motion on long and narrow substrates.

SUBMITTER: Li B

PROVIDER: S-EPMC4190608 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Coherent motions in confluent cell monolayer sheets.

Li Bo B Sun Sean X SX

Biophysical journal 20141001 7

Cell migration plays a pivotal role in many physiologically important processes such as embryogenesis, wound-healing, immune defense, and cancer metastasis. Although much effort has been directed toward motility of individual cells, the mechanisms underpinning collective cell migration remain poorly understood. Here we develop a collective motility model that incorporates cell mechanics and persistent random motions of individual cells to study coherent migratory motions in epithelial-like monol ...[more]

PMID: 25296305

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Project description:P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the apical membrane.

Dataset Information

Coherent motions in confluent cell monolayer sheets.

Publications

Coherent motions in confluent cell monolayer sheets.

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