Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.

Many fundamental cell processes, such as angiogenesis, neurogenesis and cancer metastasis, are thought to be modulated by extracellular matrix stiffness. Thus, the availability of matrix substrates having well-defined stiffness profiles can be of great importance in biophysical studies of cell-subst...

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Main Authors: Raimon Sunyer, Albert J Jin, Ralph Nossal, Dan L Sackett
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0046107&type=printable
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author Raimon Sunyer
Albert J Jin
Ralph Nossal
Dan L Sackett
author_facet Raimon Sunyer
Albert J Jin
Ralph Nossal
Dan L Sackett
author_sort Raimon Sunyer
collection DOAJ
description Many fundamental cell processes, such as angiogenesis, neurogenesis and cancer metastasis, are thought to be modulated by extracellular matrix stiffness. Thus, the availability of matrix substrates having well-defined stiffness profiles can be of great importance in biophysical studies of cell-substrate interaction. Here, we present a method to fabricate biocompatible hydrogels with a well defined and linear stiffness gradient. This method, involving the photopolymerization of films by progressively uncovering an acrylamide/bis-acrylamide solution initially covered with an opaque mask, can be easily implemented with common lab equipment. It produces linear stiffness gradients of at least 115 kPa/mm, extending from ∼1 kPa to 240 kPa (in units of Young's modulus). Hydrogels with less steep gradients and narrower stiffness ranges can easily be produced. The hydrogels can be covalently functionalized with uniform coatings of proteins that promote cell adhesion. Cell spreading on these hydrogels linearly correlates with hydrogel stiffness, indicating that this technique effectively modifies the mechanical environment of living cells. This technique provides a simple approach that produces steeper gradients, wider rigidity ranges, and more accurate profiles than current methods.
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spelling doaj-art-017d1ee47fa5467ba975a85c29aea4e12025-08-20T03:25:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4610710.1371/journal.pone.0046107Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.Raimon SunyerAlbert J JinRalph NossalDan L SackettMany fundamental cell processes, such as angiogenesis, neurogenesis and cancer metastasis, are thought to be modulated by extracellular matrix stiffness. Thus, the availability of matrix substrates having well-defined stiffness profiles can be of great importance in biophysical studies of cell-substrate interaction. Here, we present a method to fabricate biocompatible hydrogels with a well defined and linear stiffness gradient. This method, involving the photopolymerization of films by progressively uncovering an acrylamide/bis-acrylamide solution initially covered with an opaque mask, can be easily implemented with common lab equipment. It produces linear stiffness gradients of at least 115 kPa/mm, extending from ∼1 kPa to 240 kPa (in units of Young's modulus). Hydrogels with less steep gradients and narrower stiffness ranges can easily be produced. The hydrogels can be covalently functionalized with uniform coatings of proteins that promote cell adhesion. Cell spreading on these hydrogels linearly correlates with hydrogel stiffness, indicating that this technique effectively modifies the mechanical environment of living cells. This technique provides a simple approach that produces steeper gradients, wider rigidity ranges, and more accurate profiles than current methods.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0046107&type=printable
spellingShingle Raimon Sunyer
Albert J Jin
Ralph Nossal
Dan L Sackett
Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
PLoS ONE
title Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
title_full Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
title_fullStr Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
title_full_unstemmed Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
title_short Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.
title_sort fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0046107&type=printable
work_keys_str_mv AT raimonsunyer fabricationofhydrogelswithsteepstiffnessgradientsforstudyingcellmechanicalresponse
AT albertjjin fabricationofhydrogelswithsteepstiffnessgradientsforstudyingcellmechanicalresponse
AT ralphnossal fabricationofhydrogelswithsteepstiffnessgradientsforstudyingcellmechanicalresponse
AT danlsackett fabricationofhydrogelswithsteepstiffnessgradientsforstudyingcellmechanicalresponse