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Molecular Engineering of Pericellular Microniche via Biomimetic Proteoglycans Modulates Cell Mechanobiology
Journal article   Open access   Peer reviewed

Molecular Engineering of Pericellular Microniche via Biomimetic Proteoglycans Modulates Cell Mechanobiology

Elizabeth R. Kahle, Biao Han, Prashant Chandrasekaran, Evan R. Phillips, Mary K. Mulcahey, X. Lucas Lu, Michele S. Marcolongo and Lin Han
ACS nano, v 16(1), pp 1220-1230
25 Jan 2022
DOI: https://doi.org/10.1021/acsnano.1c09015
PMID: 35015500
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271520View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Chemistry Chemistry, Multidisciplinary Chemistry, Physical Materials Science Materials Science, Multidisciplinary Nanoscience & Nanotechnology Physical Sciences Science & Technology Science & Technology - Other Topics Technology
Molecular engineering of biological tissues using synthetic mimics of native matrix molecules can modulate the mechanical properties of the cellular microenvironment through physical interactions with existing matrix molecules, and in turn, mediate the corresponding cell mechanobiology. In articular cartilage, the pericellular matrix (PCM) is the immediate microniche that regulates cell fate, signaling, and metabolism. The negatively charged osmo-environment, as endowed by PCM proteoglycans, is a key biophysical cue for cell mechanosensing. This study demonstrated that biomimetic proteoglycans (BPGs), which mimic the ultrastructure and polyanionic nature of native proteoglycans, can be used to molecularly engineer PCM micromechanics and cell mechanotransduction in cartilage. Upon infiltration into bovine cartilage explant, we showed that localization of BPGs in the PCM leads to increased PCM micromodulus and enhanced chondrocyte intracellular calcium signaling. Applying molecular force spectroscopy, we revealed that BPGs integrate with native PCM through augmenting the molecular adhesion of aggrecan, the major PCM proteoglycan, at the nanoscale. These interactions are enabled by the biomimetic "bottle-brush" ultrastructure of BPGs and facilitate the integration of BPGs within the PCM. Thus, this class of biomimetic molecules can be used for modulating molecular interactions of pericellular proteoglycans and harnessing cell mechanosensing. Because the PCM is a prevalent feature of various cell types, BPGs hold promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.

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