David S. Long

Stress-related changes to immune cells in the skin prior to wounding may impair subsequent healing

Higher psychological stress is associated with slower dermal wound healing, but the immunological mechanisms behind this effect are only partially understood. This paper aims to investigate whether immune cells present in the skin prior to wounding can affect subsequent healing in high-stress and low-stress participants. Two studies are presented in which skin biopsies were analysed using immunohistochemistry for numbers of macrophages and Langerhans cells, and immune cell activation (Study 2 only). Immune cells were related to perceived stress levels and subsequent healing. Study 1 included 19 healthy older adults and showed that higher stress was associated with significantly fewer macrophages in the skin. Study 2 included 22 younger adults and showed that higher stress was associated with significantly lower activation of immune cells in the skin. Furthermore, lower activation of immune cells (as measured by human leukocyte antigen (HLA expression)) and fewer Langerhans cells were associated with slower healing. Together these studies show the first preliminary evidence that the number and activation of immune cells in the skin prior to wounding are affected by stress and can impact healing. Larger studies are needed to confirm these effects.

Computational models of the primary cilium and endothelial mechanotransmission

In endothelial cells (ECs), the mechanotransduction of fluid shear stress is partially dependent on the transmission of force from the fluid into the cell (mechanotransmission). The role of the primary cilium in EC mechanotransmission is not yet known. To motivate a framework towards quantifying cilia contribution to EC mechanotransmission, we have reviewed mechanical models of both (1) the primary cilium (three-dimensional and lower-dimensional) and (2) whole ECs (finite element, non-finite element, and tensegrity). Both the primary cilia and whole EC models typically incorporate fluid-induced wall shear stress and spatial geometry based on experimentally acquired images of cells. This paper presents future modelling directions as well as the major goals towards integrating primary cilium models into a multi-component EC mechanical model. Finally, we outline how an integrated cilium-EC model can be used to better understand mechanotransduction in the endothelium.

Mechanical Models of Endothelial Mechanotransmission Based on a Population of Cells

Computational cell mechanics models are dependent on cell morphology. Most studies of cell mechanics use an idealized geometry or a cell-specific approach. These approaches do not consider the effect of morphological variation in cell populations. In this chapter we analyze shape variation within a population of endothelial cells, and the effect this variation has on stress estimates from finite-element modeling. We developed shape descriptors to quantify variation in the nucleus and overall cell shape in a population of human microvascular endothelial cells (n = 15). From these descriptors, we generate statistically representative spatial models that more accurately reflect the cell shape of the entire population. We also generate models with non-typical morphology that are less likely to be found in the cell population. Both of these model types were subject to finite-element analysis, and compared to illustrate how morphological variation effects stress estimates.

A boundary-integral representation for biphasic mixture theory, with application to the post-capillary glycocalyx

We describe a new boundary-integral representation for biphasic mixture theory, which allows us to efficiently solve certain elastohydrodynamic–mobility problems using boundary element methods. We apply this formulation to model the motion of a rigid particle through a microtube which has non-uniform wall shape, is filled with a viscous Newtonian fluid, and is lined with a thin poroelastic layer. This is relevant to scenarios such as the transport of small rigid cells (such as neutrophils) through microvessels that are lined with an endothelial glycocalyx layer (EGL). In this context, we examine the impact of geometry upon some recently reported phenomena, including the creation of viscous eddies, fluid flux into the EGL, as well as the role of the EGL in transmitting mechanical signals to the underlying endothelial cells.

A potential role for genome structure in the translation of mechanical force during immune cell development.

ABSTRACT Immune cells react to a wide range of environments, both chemical and physical. While the former has been extensively studied, there is growing evidence that physical and in particular mechanical forces also affect immune cell behavior and development. In order to elicit a response that affects immune cell behavior or development, environmental signals must often reach the nucleus. Chemical and mechanical signals can initiate signal transduction pathways, but mechanical forces may also have a more direct route to the nucleus, altering nuclear shape via mechanotransduction. The three-dimensional organization of DNA allows for the possibility that altering nuclear shape directly remodels chromatin, redistributing critical regulatory elements and proteins, and resulting in wide-scale gene expression changes. As such, integrating mechanotransduction and genome architecture into the immunology toolkit will improve our understanding of immune development and disease.

Quantifying Cytoskeletal Morphology in Endothelial Cells to Enable Mechanical Analysis

Wall shear stress induced remodelling of endothelial cell morphology is a focal cause of atherosclerosis. While the force distribution within endothelial cells has been quantified using computational modelling, no studies have included an image-informed cytoskeleton, nor have any studies examined the effect of population variation of the cytoskeleton. In this paper we quantified the spatial variation of the cytoskeleton and primary cilium in a population of endothelial cells to enable future mechanical analysis.

Tensegrity structures - Computational and experimental tensegrity mechanics

The present paper deals with tensegrity structures. We review the definition of tensegrity structures, and describe both experimental and computational form finding methods. Also described are the numerical methods for the simulation of prestress induced stiffness, and the static and dynamic structural analyses. Furthermore, we present laboratory models and measurement methods for identifying the realized geometry and prestress state. Finally, computationally and experimentally obtained geometries and prestress states are compared, a representative realization of a real world tensegrity tower is shown and the modeling of biological cells as tensegrity structures is adressed.

A design project based approach to teaching undergraduate instrumentation

Instead of employing traditional lecture-lab pedagogy to teach undergraduate instrumentation, an open-ended group design project based approach was used. In the approach, the project was assigned to the students in the first week of lectures and served as the foundation, motivation, and context for the entire course. Each group had a project mentor. Lectures and hands-on laboratories supported the design project. The following is discussed: (1) the challenges posed by this approach; (2) recommendations for addressing these challenges; and, (3) how the course contributes towards satisfying The Institution of Professional Engineers New Zealand Graduate Competency Profiles.

Aortic Hemodynamics and Endothelial Gene Expression: An Animal Specific Approach

Atherosclerosis is a major cause of morbidity and mortality in the developed world. This disease is identified by endothelial dysfunction, inflammation and the accumulation of lipids and cellular elements within the intima of medium and large-sized arteries. Within these arteries, the distribution of atherosclerotic lesions is non-uniform; the inner wall of curved sections and the outer walls of bifurcations are susceptible sites. Evidence suggests that the focal nature of the disease is mediated in part by local fluid mechanical stresses at the interface between flowing blood and the vessel wall. Strategically located at this interface is the monolayer of cells known as the endothelium. Although it was once considered to be an inert cell layer, the endothelium is a highly complex and metabolically dynamic cell layer. As a result, local fluid mechanical stresses at the wall of arteries may alter the phenotype of endothelial cells (ECs). With that in mind, the aim of this study is to better characterize the modulation of the endothelial cell phenotype in response to blood flow induced wall shear stress (WSS).Copyright