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Ultrathin Porated Elastic Hydrogels As a Biomimetic Basement Membrane for Dual Cell Culture
Published on: December 26, 2017
The role of substratum compliance of hydrogels on vascular endothelial cell behavior
Joshua A Wood1, Nihar M Shah, Clayton T McKee
1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, 1 Shields Avenue, University of California, Davis, CA 95616, USA.
Insights
Substratum compliance, or stiffness, significantly impacts endothelial cell behaviors like attachment and migration. Understanding this mechanical cue is crucial for cardiovascular disease research and designing better medical devices.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cardiovascular Research
Background:
- Cardiovascular disease (CVD) is a major global cause of death, with significant research efforts underway.
- Knowledge gaps persist regarding CVD onset, progression, and effective therapeutic strategies.
- The influence of biophysical cues, particularly extracellular matrix stiffness, on endothelial cells is understudied.
Purpose of the Study:
- To investigate the impact of substratum compliance on human primary endothelial cell behaviors.
- To explore endothelial cell heterogeneity in response to varying mechanical cues.
- To highlight the importance of mechanical properties in endothelial cell function.
Main Methods:
- Cultured diverse human primary endothelial cell types on substrates with varying compliance.
- Substrate stiffness ranged across values reported for the vascular endothelial basement membrane.
- Assessed cell attachment, spreading, elongation, proliferation, and migration.
Main Results:
- Substratum compliance profoundly affected endothelial cell attachment, spreading, elongation, proliferation, and migration.
- Different endothelial cell populations exhibited distinct responses to changes in substratum compliance.
- Documented significant endothelial heterogeneity in response to biophysical cues.
Conclusions:
- Substratum compliance is a critical factor modulating endothelial cell behavior.
- Endothelial cell responses to mechanical cues are heterogeneous.
- Incorporating substratum compliance is essential for accurate in vitro models and prosthetic design.
- Altered vascular substratum compliance may play a role in cardiovascular disease development and progression.
Abstract:
Cardiovascular disease (CVD) remains a leading cause of death both within the United States (US) as well as globally. In 2006 alone, over one-third of all deaths in the US were attributable to CVD. The high prevalence, mortality, morbidity, and socioeconomic impact of CVD has motivated a significant research effort; however, there remain significant knowledge gaps regarding disease onset and progression as well as pressing needs for improved therapeutic approaches. One critical area of research that has received limited attention is the role of biophysical cues on the modulation of endothelial cell behaviors; specifically, the impact of local compliance, or the stiffness, of the surrounding vascular endothelial extracellular matrix. In this study, the impact of substratum compliance on the modulation of cell behaviors of several human primary endothelial cell types, representing different anatomic sites and differentiation states in vivo, were investigated. Substrates used within our studies span the range of compliance that has been reported for the vascular endothelial basement membrane. Differences in substratum compliance had a profound impact on cell attachment, spreading, elongation, proliferation, and migration. In addition, each cell population responded differentially to changes in substratum compliance, documenting endothelial heterogeneity in the response to biophysical cues. These results demonstrate the importance of incorporating substratum compliance in the design of in vitro experiments as well as future prosthetic design. Alterations in vascular substratum compliance directly influence endothelial cell behavior and may participate in the onset and/or progression of CVDs.
