Abstract
The migration behaviors of cancer cells are known to be heterogeneous. However, the interplay between the adhesion interactions, dynamical shape changes and fluid flows in regulating cell migration heterogeneity and plasticity during cancer metastasis is still elusive. To further quantitative understanding of cell motility and morphology, we develop a theory using stochastic quantization method that describes the role of biophysical cues in regulating diverse cell motility. We show that the cumulative effect of time dependent adhesion interactions that determine the structural rearrangements and self-generated force due to actin remodeling, dictate the super-diffusive motion of mesenchymal phenotype in the absence of flow. Interstitial flows regulate cell motility phenotype and promote the amoeboid over mesenchymal motility through adhesion interactions. Cells exhibit a dynamical slowing down of collective migration, with a decreasing degree of super-diffusion. Mesenchymal cells are more persistent and diffusive compared to amoeboid cells. Our findings, suggest a mechanism of Interstitial flow induced directed motion of cancer cells through adhesion, and provide the much needed insight into a recent experimental observation concerning the diverse motility of breast cancer cells.
Highlights
Collective cancer cell invasion, followed by local and distant metastasis, is a hallmark of cancer [1]
Dynamics associated with invasion and metastasis involve the collective cell migration regulated by biomechanical and biophysical cues [12,13,14,15,16]
In the present contribution, using a theoretical framework, we provide insight into the dynamics of a colony of cancer cells driven by biophysical cues
Summary
Collective cancer cell invasion, followed by local and distant metastasis, is a hallmark of cancer [1]. Dynamics associated with invasion and metastasis involve the collective cell migration regulated by biomechanical (e.g., cytokines secreted by cells and nutrients) and biophysical cues (e.g., fluid flows and extracellular matrix) [12,13,14,15,16]. We show how the time scale of attachment is reduced by flow-induced sweeping away the fibronectin (FN) molecules and cells exhibit amoeboid motility phenotype. Mesenchymal migration is characterized by an elongated fibroblastlike morphology, highly condensed cell-matrix adhesions, and formation of contractile actomyosin bundles [37]. Amoeboid migration is characterized by a rounded morphology, formation of bleblike protrusions, restriction of actomyosin contractility to the cell cortex, and transient, shortlived adhesions with the ECM, and squeezing through the matrix pore when finding a suitable path [30,37]. The flows carried away the cell-secreted adhesion molecules before they were assembled into fibrils and anchored to the collagen fibers [30]
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