Journal article
Nonlinear Strain Stiffening Is Not Sufficient to Explain How Far Cells Can Feel on Fibrous Protein Gels
Biophysical journal, Vol.105(1), pp.11-20
07/02/2013
DOI: 10.1016/j.bpj.2013.05.032
PMCID: PMC3699756
PMID: 23823219
Abstract
Recent observations suggest that cells on fibrous extracellular matrix materials sense mechanical signals over much larger distances than they do on linearly elastic synthetic materials. In this work, we systematically investigate the distance fibroblasts can sense a rigid boundary through fibrous gels by quantifying the spread areas of human lung fibroblasts and 3T3 fibroblasts cultured on sloped collagen and fibrin gels. The cell areas gradually decrease as gel thickness increases from 0 to 150
μ
m, with characteristic sensing distances of >65
μ
m below fibrin and collagen gels, and spreading affected on gels as thick as 150
μ
m. These results demonstrate that fibroblasts sense deeper into collagen and fibrin gels than they do into polyacrylamide gels, with the latter exhibiting characteristic sensing distances of <5
μ
m. We apply finite-element analysis to explore the role of strain stiffening, a characteristic mechanical property of collagen and fibrin that is not observed in polyacrylamide, in facilitating mechanosensing over long distances. Our analysis shows that the effective stiffness of both linear and nonlinear materials sharply increases once the thickness is reduced below 5
μ
m, with only a slight enhancement in sensitivity to depth for the nonlinear material at very low thickness and high applied traction. Multiscale simulations with a simplified geometry predict changes in fiber alignment deep into the gel and a large increase in effective stiffness with a decrease in substrate thickness that is not predicted by nonlinear elasticity. These results suggest that the observed cell-spreading response to gel thickness is not explained by the nonlinear strain-stiffening behavior of the material alone and is likely due to the fibrous nature of the proteins.
Details
- Title: Subtitle
- Nonlinear Strain Stiffening Is Not Sufficient to Explain How Far Cells Can Feel on Fibrous Protein Gels
- Creators
- Mathilda S Rudnicki - Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MassachusettsHeather A Cirka - Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MassachusettsMaziar Aghvami - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaEdward A Sander - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaQi Wen - Department of Physics, Worcester Polytechnic Institute, Worcester, MassachusettsKristen L Billiar - Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.105(1), pp.11-20
- DOI
- 10.1016/j.bpj.2013.05.032
- PMID
- 23823219
- PMCID
- PMC3699756
- NLM abbreviation
- Biophys J
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Publisher
- The Biophysical Society
- Language
- English
- Date published
- 07/02/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Chemical and Biochemical Engineering
- Record Identifier
- 9984064566702771
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