Equilibrium Modeling of the Mechanics and Structure of the Cancer Glycocalyx

Abstract

The glycocalyx is a thick coat of proteins and carbohydrates on the outer surface of all eukaryotic cells. Overproduction of large, flexible or rod-like biopolymers, including hyaluronic acid and mucins, in the glycocalyx strongly correlates with the aggression of many cancer types. However, theoretical frameworks to predict the effects of these changes on cancer cell adhesion and other biophysical processes remain limited. Here, we propose a detailed modeling framework for the glycocalyx incorporating important physical effects of biopolymer flexibility, excluded volume, counterion mobility, and coupled membrane deformations. Because mucin and hyaluronic biopolymers are proposed to extend and rigidify depending on the extent of their decoration with side chains, we propose and consider two limiting cases for the structural elements of the glycocalyx: stiff beams and flexible chains. Simulations predict the mechanical response of the glycocalyx to compressive loads, which are imposed on cells residing in the highly confined spaces of the solid tumor or invaded tissues. Notably, the shape of the mechanical response transitions from hyperbolic to sigmoidal for more rod-like glycocalyx elements. These mechanical responses, along with the corresponding equilibrium protein organizations and membrane topographies, are summarized to aid in hypothesis generation and the evaluation of future experimental measurements. Overall, the modeling framework developed provides a theoretical basis for understanding the physical biology of the glycocalyx in human health.

Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data

“…It is important to note, our results found at concentrations above 6.25 × 10 –4 U/ml are well in line with previous findings on adhesion strength, but the kinetics of adhesion was not investigated previously. For example, experiments performed by Gandhi et al 77 on melanoma cells by digesting chondroitin sulfate and dermatan sulfate chains with chondroitinase AC and chondroitinase B fit to our result. The applied treatment inhibited the angiogenesis, proliferation, and invasion of melanoma cells.…”

Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis

“…Furthermore, we can speculate that myotubes may be protected by a mechanical buffer layer composed of e.g. large glycocalyx biopolymers that are known to have crucial mechanical functions for cells and cell aggregates [17]. Our results suggest that cellular tension within in vitro muscle tissues is more connected to tissue pre-tension.…”

The Emerging Role of the Mammalian Glycocalyx in Functional Membrane Organization and Immune System Regulation

“…It should be emphasized that this regulation of cell membrane morphology is an excellent example for an important motive: The glycocalyx frequently (although not exclusively) acts via physical interactions. Steric effects, molecular crowding, electrostatic effects (e.g., repulsion of sulfated sugars and counter ion trapping), multivalency effects, size exclusion, and others are phenomena which play a key role in glycocalyx biology (Kuo et al, 2018;Gandhi et al, 2019). Characteristically, each instance of the listed phenomena exerts only a small force on the system, but due to the large dimensions of the glycocalyx, many small forces add up to a significant total force, having a considerable effect on the cellular state.…”