Cell focal adhesion clustering leads to decreased and homogenized basal strains.

The subendothelial matrix of the artery is a complex mechanical environment where endothelial cells respond to and affect changes upon the underlying substrate. Our recent work has demonstrated that endothelial cell strain heterogeneity increases on a more heterogeneous underlying subendothelial matrix, and these cells display increased focal adhesion presence on stiffer substrate areas. However, the impact of these grouped focal adhesions on endothelial cell strains has not been explored.

Beneficial Effects of Exercise on Subendothelial Matrix Stiffness are Short-Lived.

Aerobic exercise helps to maintain cardiovascular health in part by mitigating age-induced arterial stiffening. However, the long-term effects of exercise regimens on aortic stiffness remain unknown, especially in the intimal extracellular matrix layer known as the subendothelial matrix. To examine how the stiffness of the subendothelial matrix changes following exercise cessation, mice were exposed to an 8 week swimming regimen followed by an 8 week sedentary rest period.

High-Fat, High-Sugar Diet-Induced Subendothelial Matrix Stiffening is Mitigated by Exercise.

Consumption of a high-fat, high-sugar diet and sedentary lifestyle are correlated with bulk arterial stiffening. While measurements of bulk arterial stiffening are used to assess cardiovascular health clinically, they cannot account for changes to the tissue occurring on the cellular scale. The compliance of the subendothelial matrix in the intima mediates vascular permeability, an initiating step in atherosclerosis.

Mechanical heterogeneities in the subendothelial matrix develop with age and decrease with exercise.

Arterial stiffening occurs with age and is associated with lack of exercise. Notably both age and lack of exercise are major cardiovascular risk factors. While it is well established that bulk arterial stiffness increases with age, more recent data suggest that the intima, the innermost arterial layer, also stiffens during aging.

Self-Assembled Cationic Biodegradable Nanoparticles from pH-Responsive Amino-Acid-Based Poly(Ester Urea Urethane)s and Their Application As a Drug Delivery Vehicle.

The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks.

Age-related vascular stiffening: causes and consequences.

Arterial stiffening occurs with age and is closely associated with the progression of cardiovascular disease. Stiffening is most often studied at the level of the whole vessel because increased stiffness of the large arteries can impose increased strain on the heart leading to heart failure. Interestingly, however, recent evidence suggests that the impact of increased vessel stiffening extends beyond the tissue scale and can also have deleterious microscale effects on cellular function.

Biophysical induction of vascular smooth muscle cell podosomes.

Vascular smooth muscle cell (VSMC) migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP) secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu), however little is known about the physiological cues that drive podosome formation.

Cooperative effects of matrix stiffness and fluid shear stress on endothelial cell behavior.

Arterial hemodynamic shear stress and blood vessel stiffening both significantly influence the arterial endothelial cell (EC) phenotype and atherosclerosis progression, and both have been shown to signal through cell-matrix adhesions. However, the cooperative effects of fluid shear stress and matrix stiffness on ECs remain unknown. To investigate these cooperative effects, we cultured bovine aortic ECs on hydrogels matching the elasticity of the intima of compliant, young, or stiff, aging arteries.

Eliminating adhesion errors in nanoindentation of compliant polymers and hydrogels.

Nanoindentation is a valuable tool for characterization of biomaterials due to its ability to measure local properties in heterogeneous, small or irregularly shaped samples. However, applying nanoindentation to compliant, hydrated biomaterials leads to many challenges including adhesion between the nanoindenter tip and the sample. Although adhesion leads to overestimation of the modulus of compliant samples when analyzing nanoindentation data using traditional analysis techniques, most studies of biomaterials have ignored its effects.