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Astrocytes are essential to brain homeostasis and their dysfunction can have devastating consequences on human quality of life. Such deleterious effects are generally due in part to changes that occur at the cellular level, which may be biochemical or biomechanical in nature. One biomechanical change that can occur is a change in tissue stiffness. Brain tumors are generally associated with increased brain tissue stiffness, but the impact increased tissue stiffness has on astrocyte biomechanical behavior is poorly understood. Therefore, in this study we cultured human astrocytes on flexible substrates with stiffness that mimicked the healthy human brain (1 kPa), meningioma (4 kPa), and glioma (11 kPa) and investigated astrocyte biomechanical behavior by measuring cell-substrate tractions, strain energies, cell-cell intercellular stresses, and cellular velocities. In general, tractions, intercellular stresses, and strain energy was observed to increase as a function of increased substrate stiffness, while cell velocities were observed to decrease with increased substrate stiffness. We believe this study will be of great importance to the fields of brain pathology and brain physiology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lab-on-a-chip technologies have allowed researchers to acquire a flexible, yet relatively inexpensive testbed to study one of the leading causes of death worldwide, cardiovascular disease. Cardiovascular diseases, such as peripheral artery disease, arteriosclerosis, and aortic stenosis, for example, have all been studied by lab-on-a-chip technologies. These technologies allow for the integration of mammalian cells into functional structures that mimic vital organs with geometries comparable to those found in vivo. For this review, we focus on microdevices that have been developed to study cardiovascular physiology and pathology. With these technologies, researchers can better understand the electrical-biomechanical properties unique to cardiomyocytes and better stimulate and understand the influence of blood flow on the human vasculature. Such studies have helped increase our understanding of many cardiovascular diseases in general; as such, we present here a review of the current state of the field and potential for the future.

Microfluidic technologies are frequently employed as point-of-care diagnostic tools for improving time-to-diagnosis and improving patient outcomes in clinical settings. These microfluidic devices often are designed to operate with peripheral equipment for liquid handling that increases the cost and complexity of these systems and reduces their potential for widespread adoption in low resource healthcare applications. Here, we present a low-cost (~$120), open-source peristaltic pump constructed with a combination of three dimensional (3D)-printed parts and common hardware, which is amenable to deployment with microfluidic devices for point-of-care diagnostics. This pump accepts commonly available silicone rubber tubing in a range of sizes from 1.5 to 3 mm, and is capable of producing flow rates up to 1.6 mL min -1 . This device is programmed with an Arduino microcontroller, allowing for custom flow profiles to fit a wide range of low volume liquid handling applications including precision liquid aliquoting, flow control within microfluidics, and generation of physiologically relevant forces for studying cellular mechanobiology within microfluidic systems.

Blood vessels may be found throughout the entire body and their importance to human life is undeniable. This is evident in the fact that a malfunctioning blood vessel can result in mild symptoms such as shortness of breath or chest pain to more severe symptoms such as a heart attack or stroke, to even death in the severest of cases. Furthermore, there are a host of pathologies that have been linked to the human vasculature. As a result many researchers have attempted to unlock the mysteries of the vasculature by performing studies that duplicate the physiological structural, chemical, and mechanical properties known to exist. While the ideal study would consist of utilizing living, blood vessels derived from human tissue, such studies are not always possible since intact human blood vessels are not readily accessible and there are immense technical difficulties associated with such studies. These limitations have opened the door for the development of microdevices modeled after the human vasculature as it is believed by many researchers in the field that such devices can one day replace tissue models. In this review we present an overview of microdevices developed to mimic various types of vasculature found throughout the human body. Although the human body contains a diverse array of vascular systems for this review we limit our discussion to the cardiovascular system and cerebrovascular system and discuss such systems that have been fabricated in both 2D and 3D configurations.

Mechanobiology involves the investigation of mechanical forces and their effect on the development, physiology, and pathology of biological systems. The human body has garnered much attention from many groups in the field, as mechanical forces have been shown to influence almost all aspects of human life ranging from breathing to cancer metastasis. Beyond being influential in human systems, mechanical forces have also been shown to impact nonhuman systems such as algae and zebrafish. Studies of nonhuman and human systems at the cellular level have primarily been done in two-dimensional (2D) environments, but most of these systems reside in three-dimensional (3D) environments. Furthermore, outcomes obtained from 3D studies are often quite different than those from 2D studies. We present here an overview of a select group of human and nonhuman systems in 2D and 3D environments. We also highlight mechanobiological approaches and their respective implications for human and nonhuman physiology.

From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems-both inert and living-have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell-cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role.

Endothelial cell alignment along the direction of laminar fluid flow is widely understood to be a defining morphological feature of vascular homeostasis. While the role of associated signaling and structural events have been well studied, associated intercellular stresses under laminar fluid shear have remained ill-defined and the role of these stresses in the alignment process has remained obscure. To fill this gap, we report here the tractions as well as the complete in-plane intercellular stress fields measured within the human umbilical vein endothelial cell (HUVEC) monolayer subjected to a steady laminar fluid shear of 1 Pa. Tractions, intercellular stresses, as well as their time course, heterogeneity, and anisotropy, were measured using monolayer traction microscopy and monolayer stress microscopy. Prior to application of laminar fluid flow, intercellular stresses were largely tensile but fluctuated dramatically in space and in time (317 ± 122 Pa). Within 12 h of the onset of laminar fluid flow, the intercellular stresses decreased substantially but continued to fluctuate dramatically (142 ± 84 Pa). Moreover, tractions and intercellular stresses aligned strongly and promptly (within 1 h) along the direction of fluid flow, whereas the endothelial cell body aligned less strongly and substantially more slowly (12 h). Taken together, these results reveal that steady laminar fluid flow induces prompt reduction in magnitude and alignment of tractions and intercellular stress tensor components followed by the retarded elongation and alignment of the endothelial cell body. Appreciably smaller intercellular stresses supported by cell-cell junctions logically favor smaller incidence of gap formation and thus improved barrier integrity., (Copyright © 2015 the American Physiological Society.)