Introducing the Modeling Cell Proliferation and the Cell Microenvironment Collection

In 2020, PLOS ONE announced a Call for Papers on Modeling Cell Proliferation and the Cell Microenvironment. This week, we celebrate the launch of this collection, which includes a number of papers offering new insights into this vital topic. Understanding the cellular microenvironment and how cells proliferate has a number of useful applications, and this collection showcases the breadth of this research area. We are immensely grateful to Guest Editors Aurélie Carlier (Maastricht University), Ravi Iyengar (Icahn School of Medicine at Mount Sinai), Padmini Rangamani (University of California, San Diego) and Vivek Shenoy (University of Pennsylvania), who were instrumental in curating this collection at PLOS ONE.

Bacterial biofilms are present in many different environments, and are important to understand both in order to utilize their properties as well as combating them in problematic settings. Jin and Marshall extend an existing model of biofilm formation to study for the first time how the fimbrial force and extracellular polymeric substance (EPS) flow affect the growth of biofilms. The model incorporates both continuous elements, for modeling the water and EPS, and discrete elements, for modeling the interaction between individual cells. They find that the total cell number is a main driver for colony morphology, and the findings are in good agreement with existing experimental work. The study concludes that the ultimate structure of a bacterial colony is dependent on the interaction of the opposing effects of cell drag from EPS production and the fimbrial force.

The forces that are exerted by cells play a major role in the mechanisms by which cancer metastasis, angiogenesis and other processes operate. Hervas-Rayul and colleagues explore cell surface traction through an experimental study followed by solving the inverse problem iteratively using a finite element model. The model utilizes the displacement field for 3D traction force microscopy as an input for the inverse problem solver. In this way, this study provides a concrete link between experimental and modeling work in the field, and can be applied to any material and geometry.

The shape of a cell is influenced both by its cytoskeleton and the surrounding environment. In a new study, Eroumé and colleagues model the effect of cell shape on cell polarization, specifically by studying how cell shape influences Cdc42 patterns. They find that cell shape and aspect ratio both influence Cdc42 patterns, and that some of these influences are non-intuitive. They find evidence for ‘reverse polarization’ in which the maximal Cdc42 concentration can shift in the direction opposite the initial polarization gradient. Their results call for future experimental validation of the predictions that come out of this work.

Metastasis can arise when circulating tumor cells are transported through the bloodstream to a new secondary location. Understanding how this process works can aid the development of various therapies that block the transport of these circulating tumor cells both as single cells and as clusters. In an effort to study these processes in more detail, Marrella and colleagues have developed a microfluidic device which mimics the wall shear stress experienced in the human vascular system. The device is 3D-printed using a biocompatible photopolymer resin, and their investigations show how increasing wall shear stress can influence morphology and disaggregation of cell clusters.

Uncontrolled cell proliferation is a major factor in tumor growth and progression of colorectal cancer. Vundavilli and colleagues present new results on the underlying mutations that may be influencing colorectal cancer cell proliferation through mathematical and experimental work. They use publicly available gene expression data to identify pathways and mutations that are deregulated in colon cancer, and then apply Boolean modeling to search for drug combinations that may induce cancer cell death.

Taken together, these papers provide new insights into cell signaling, biofilms and cancer metastasis, and provide suggestions for future lines of research within these broader research areas. We will add papers to this collection over time as they are published, so please do keep checking back.

References:

Eroumé K, Vasilevich A, Vermeulen S, de Boer J, Carlier A (2021) On the influence of cell shape on dynamic reaction-diffusion polarization patterns. PLoS ONE 16(3): e0248293. https://doi.org/10.1371/journal.pone.0248293

Hervas-Raluy S, Gomez-Benito MJ, Borau-Zamora C, Cóndor M, Garcia-Aznar JM (2021) A new 3D finite element-based approach for computing cell surface tractions assuming nonlinear conditions. PLoS ONE 16(4): e0249018. https://doi.org/10.1371/journal.pone.0249018

Jin X, Marshall JS (2020) Mechanics of biofilms formed of bacteria with fimbriae appendages. PLoS ONE 15(12): e0243280. https://doi.org/10.1371/journal.pone.0243280

Marrella A, Fedi A, Varani G, Vaccari I, Fato M, Firpo G, et al. (2021) High blood flow shear stress values are associated with circulating tumor cells cluster disaggregation in a multi-channel microfluidic device. PLoS ONE 16(1): e0245536. https://doi.org/10.1371/journal.pone.0245536

Vundavilli H, Datta A, Sima C, Hua J, Lopes R, Bittner M (2021) Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. PLoS ONE 16(2): e0247190. https://doi.org/10.1371/journal.pone.0247190

Image attribution: Ricardo Murga and Rodney Donlan, Public domain, via Wikimedia Commons