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Metropolitan Government of Nashville-Davidson (balance), TN, United States

Potdar A.A.,Vanderbilt University | Potdar A.A.,Vanderbilt Integrative Cancer Biology Center | Jeon J.,Vanderbilt University | Jeon J.,Vanderbilt Integrative Cancer Biology Center | And 7 more authors.
PLoS ONE | Year: 2010

Background: Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells) that exist in multi-cellular organisms (humans) follow a bimodal correlated random walk (BCRW). Methodology/Principal Findings: Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases) each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation). Conclusions/Significance: Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model. © 2010 Potdar et al.

Potdar A.A.,Vanderbilt Integrative Cancer Biology Center | Potdar A.A.,University of Connecticut | Jeon J.,Vanderbilt Integrative Cancer Biology Center | Jeon J.,University of Connecticut | And 10 more authors.
Biophysical Journal | Year: 2010

Cell motility is a fundamental process with relevance to embryonic development, immune response, and metastasis. Cells move either spontaneously, in a nondirected fashion, or in response to chemotactic signals, in a directed fashion. Even though they are often studied separately, both forms of motility share many complex processes at the molecular and subcellular scale, e.g., orchestrated cytoskeletal rearrangements and polarization. In addition, at the cellular level both types of motility include persistent runs interspersed with reorientation pauses. Because there is a great range of variability in motility among different cell types, a key challenge in the field is to integrate these multiscale processes into a coherent framework. We analyzed the motility of Dictyostelium cells with bimodal analysis, a method that compares time spent in persistent versus reorientation mode. Unexpectedly, we found that reorientation time is coupled with persistent time in an inverse correlation and, surprisingly, the inverse correlation holds for both nondirected and chemotactic motility, so that the full range of Dictyostelium motility can be described by a single scaling relationship. Additionally, we found an identical scaling relationship for three human cell lines, indicating that the coupling of reorientation and persistence holds across species and making it possible to describe the complexity of cell motility in a surprisingly general and simple manner. With this new perspective, we analyzed the motility of Dictyostelium mutants, and found four in which the coupling between two modes was altered. Our results point to a fundamental underlying principle, described by a simple scaling law, unifying mechanisms of eukaryotic cell motility at several scales. © 2010 by the Biophysical Society.

Jeon J.,Vanderbilt University | Jeon J.,Vanderbilt Integrative Cancer Biology Center | Quaranta V.,Vanderbilt Integrative Cancer Biology Center | Quaranta V.,Vanderbilt University | And 3 more authors.
Biophysical Journal | Year: 2010

We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of tumor growth and invasion. The continuum part of the OLHDC model describes microenvironmental components such as matrix-degrading enzymes, nutrients or oxygen, and extracellular matrix (ECM) concentrations, whereas the discrete portion represents individual cell behavior such as cell cycle, cell-cell, and cell-ECM interactions and cell motility by the often-used persistent random walk, which can be depicted by the Langevin equation. Using this framework of the OLHDC model, we develop a phenomenologically realistic and bio/physically relevant model that encompasses the experimentally observed superdiffusive behavior (at short times) of mammalian cells. When systemic simulations based on the OLHDC model are performed, tumor growth and its morphology are found to be strongly affected by cell-cell adhesion and haptotaxis. There is a combination of the strength of cell-cell adhesion and haptotaxis in which fingerlike shapes, characteristic of invasive tumor, are observed. © 2010 by the Biophysical Society.

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