Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells.

Mechanical signals regulate blood vessel development in vivo, and have been demonstrated to regulate signal transduction of endothelial cell (EC) and smooth muscle cell (SMC) phenotype in vitro. However, it is unclear how the complex process of angiogenesis, which involves multiple cell types and growth factors that act in a spatiotemporally regulated manner, is triggered by a mechanical input. Here, we describe a mechanism for modulating vascular cells during sequential stages of an in vitro model of early angiogenesis by applying cyclic tensile strain. Cyclic strain of human umbilical vein (HUV)ECs up-regulated the secretion of angiopoietin (Ang)-2 and PDGF-betabeta, and enhanced endothelial migration and sprout formation, whereas effects were eliminated with shRNA knockdown of endogenous Ang-2. Applying strain to colonies of HUVEC, cocultured on the same micropatterned substrate with nonstrained human aortic (HA)SMCs, led to a directed migration of the HASMC toward migrating HUVECs, with diminished recruitment when PDGF receptors were neutralized. These results demonstrate that a singular mechanical cue (cyclic tensile strain) can trigger a cascade of autocrine and paracrine signaling events between ECs and SMCs critical to the angiogenic process.

Deformation and failure of protein materials in physiologically extreme conditions and disease.

Biological protein materials feature hierarchical structures that make up a diverse range of physiological materials. The analysis of protein materials is an emerging field that uses the relationships between biological structures, processes and properties to probe deformation and failure phenomena at the molecular and microscopic level. Here we discuss how advanced experimental, computational and theoretical methods can be used to assess structure-process-property relations and to monitor and predict mechanisms associated with failure of protein materials. Case studies are presented to examine failure phenomena in the progression of disease. From this materials science perspective, a de novo basis for understanding biological processes can be used to develop new approaches for treating medical disorders. We highlight opportunities to use knowledge gained from the integration of multiple scales with physical, biological and chemical concepts for potential applications in materials design and nanotechnology.

Cellular strain assessment tool (CSAT): precision-controlled cyclic uniaxial tensile loading.

The development of a multi-sample strain device and elastomeric culture wells designed to systematically assess strain effects on cell cultures is presented in this report. This device enables one to precisely conduct experimental analyses in sterile conditions while delivering cyclic uniaxial tensile strain. The input to the computer interface allows one to alter variables of frequency, duration, and amplitude of strain. The influence of strain on the migration of human umbilical vein endothelial cell (HUVEC) cultured on 2D polydimethylsiloxane (PDMS) surfaces was examined to verify the utility of this system.

Mechanical strain regulates endothelial cell patterning in vitro.

Blood vessels of the vertebrate circulatory system typically exhibit tissue-specific patterning. However, the cues that guide the development of these patterns remain unclear. We investigated the effect of cyclic uniaxial strain on vascular endothelial cell dynamics and sprout formation in vitro in two-dimensional (2D) and three-dimensional (3D) culture systems under the influence of growth factors. Cells preferentially aligned and moved in the direction perpendicular to the major strain axis in monolayer culture, and mechanical strain also regulated the spatial location of cell proliferation in 2D cell culture. Cells in 3D cell culture could be induced to form sprouts by exposure to appropriate growth factor combinations (vascular endothelial growth factor and hepatocyte growth factor), and the strain direction regulated the directionality of this process. Moreover, cyclic uniaxial strain inhibited branching of the structures formed by endothelial cells and increased their thickness. Taken together, these data support the importance of external mechanical stimulation in the regulation of endothelial cell migration, proliferation, and differentiation into primitive vessels.

How protein materials balance strength, robustness, and adaptability.

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design.