Biology subjects

Andasari, V.

Publications and source records attributed to Andasari, V..

3 recordsLinked to original sources

bioRxiv2025

Mathematical Modeling of Cancer Cell Invasion of Tissue: Development of an in silico Organotypic Assay

BackgroundOrganotypic assays are three-dimensional in vitro models widely used in cancer research to mimic the in vivo extracellular matrix (ECM) and to study cancer cell invasion by allowing investigation of critical interactions between tumor cells and their microenvironment. During invasion, cancer cells undergo genetic and epigenetic changes that disrupt cell-cell adhesion, enabling detachment from the primary tumor. Subsequently, invasive cells must (i) breach the basement membrane, a dense protein meshwork that restricts cell movement, and (ii) migrate through the surrounding ECM. This process relies on proteolytic enzyme secretion to degrade structural barriers, followed by cell-matrix adhesion-mediated migration. MethodsWe present an in silico model of cancer cell invasion in organotypic assays. The model is formulated as a system of partial differential equations capturing spatiotemporal dynamics, with nonlocal terms representing preferential adhesion-driven movement. Key variables in the model are cancer cells, proteolytic enzymes, and the ECM. ResultsComputational simulations demonstrate that modulation of cell-cell and cell-matrix adhesion parameters significantly influences tumor invasiveness. This result is consistent with experimental observations, demonstrating the models ability to accurately reflect in vitro behavior.

biophysics↗

bioRxiv2025

Delayed Extracellular Matrix Negative Feedback Contributes to Nascent Adhesion Dynamics: Mathematical Modeling and Analysis

AO_SCPLOWBSTRACTC_SCPLOWCell migration, both in vivo and in vitro, is a complex process governed by mechano-chemical interactions between cells and the extracellular matrix (ECM). These interactions, mediated by cell membrane receptors called integrins, involve bidirectional signaling between the intracellular actin cytoskeleton and the ECM. Integrins bind with cytoplasmic proteins to form adhesion complexes of varying sizes and maturity, which play crucial roles in cellular processes such as cell migration. Among these complexes are nascent adhesions-the smallest and earliest observable structures that emerge within the lamellipodium and are associated with rapid cell motility. While other adhesion types have been extensively studied, the mechanisms regulating nascent adhesions remain poorly understood. Here, we develop a mathematical model describing the bidirectional signaling between the actin cytoskeleton and ECM that controls nascent adhesion dynamics. Our framework employs a system of delay differential equations to capture the temporal coupling between actin polymerization-driven adhesion formation and force-dependent ECM displacement. The model demonstrates that nascent adhesions, initiated by actin polymerization, exert forces on the ECM, whose delayed displacement provides negative feedback that limits adhesion growth. Numerical simulations reveal that this delayed ECM feedback mechanism reproduces the characteristic lifetime and dynamics of nascent adhesions, with quantitative agreement with experimental observations. Our results suggest that delayed ECM negative feedback is a key regulator of nascent adhesion turnover, providing new insights into the spatiotemporal control of cell migration.

biophysics↗

bioRxiv2022

Multiscale Modeling of MT1-MMP-Mediated Cell Migration: Destabilization of Cell-Matrix Adhesion

One of several ways MT1-MMP promotes cell migration is by modifying cell adhesion properties. MT1-MMP directly processes cell adhesion properties by shedding cell transmembrane receptors that attach cells to the extracellular matrix (ECM). The shedding leads to the destabilization and disassembly of firm cell-matrix adhesion that holds cells in their stationary position, prompting cells to migrate. In this paper, we present a multiscale mathematical model of single cell migration driven by MT1-MMP destabilization of cell-matrix adhesion. The dynamics of MT1-MMP are modeled using a system of differential equations that are integrated with the Cellular Potts Model (CPM) for a combined modeling at the intracellular and cellular scale, respectively. The CPM is extended to include a local feedback mechanism from MT1-MMP on the membrane that enhances cell membrane fluctuations, resulting in actively migrating cells. The results of computational simulation show that MT1-MMP is capable of destabilizing strong cell-matrix adhesion and stimulating cell migration, and at the same time, also producing cell polarization and motile cell morphology.

biophysics↗