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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Gandhi JG,Koch DL,Paszek MJdoi
10.1016/j.bpj.2018.12.023subject
Has Abstractpub_date
2019-02-19 00:00:00pages
694-708issue
4eissn
0006-3495issn
1542-0086pii
S0006-3495(19)30030-Xjournal_volume
116pub_type
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