Inherent interfacial mechanical gradients in 3D hydrogels influence tumor cell behaviors.

PloS One
Shreyas S RaoJessica O Winter

Abstract

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit...Continue Reading

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Citations

Sep 21, 2013·Tissue Engineering. Part B, Reviews·Shreyas S RaoJessica O Winter
Sep 10, 2013·ACS Applied Materials & Interfaces·Shreyas S RaoJessica O Winter
Feb 3, 2015·Critical Reviews in Biotechnology·Lin WangFeng Xu
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Sep 10, 2015·IEEE Transactions on Nanobioscience·Giuliano MazziniSabina Merlo
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Oct 30, 2016·Journal of Cellular Physiology·Maddaly RaviAishwarya Pattabhi
Jul 11, 2020·Nature Reviews. Materials·Kayla J WolfSanjay Kumar
Feb 22, 2017·Macromolecular Bioscience·Aaron R ShortJessica O Winter
Jan 18, 2020·Journal of Biomedical Science·Wei-Wen Liu, Pai-Chi Li
Apr 24, 2019·Nanomaterials·Mark A CalhounJessica O Winter
Jul 19, 2013·Molecular Cancer Research : MCR·Leo S Payne, Paul H Huang
Apr 2, 2019·Colloids and Surfaces. B, Biointerfaces·Shalini R Unnikandam VeettilIan C Schneider

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Methods Mentioned

BETA
fluorescence microscopy
optical tweezers

Software Mentioned

ABAQUS CAE
ImageJ Volume Viewer Plugin
ImageJ
NIH Image J
NIH
Track J
JMP

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