Mathematical modeling of the dynamic mechanical behavior of neighboring sarcomeres in actin stress fibers

pre-printActin stress fibers (SFs) in live cells consist of series of dynamic individual sarcomeric units. Within a group of consecutive SF sarcomeres, individual sarcomeres can spontaneously shorten or lengthen without changing the overall length of this group, but the underlying mechanism is unclear. We used a computational model to test our hypothesis that this dynamic behavior is inherent to the heterogeneous mechanical properties of the sarcomeres and the cytoplasmic viscosity. Each sarcomere was modeled as a discrete element consisting of an elastic spring, a viscous dashpot and an active contractile unit all connected in parallel, and experiences forces as a result of actin filament elastic stiffness, myosin II contractility, internal viscoelasticity, or cytoplasmic drag. When all four types of forces are considered, the simulated dynamic behavior closely resembles the experimental observations, which include a low-frequency fluctuation in individual sarcomere length and compensatory lengthening and shortening of adjacent sarcomeres. Our results suggest that heterogeneous stiffness and viscoelasticity of actin fibers, heterogeneous myosin II contractility, and the cytoplasmic drag are sufficient to cause spontaneous fluctuations in SF sarcomere length. Our results shed new light to the dynamic behavior of SF and help design experiments to further our understanding of SF dynamics

A study on the modulation of alpha-actinin and filamentous actin

Cells use actin to provide structure and stability to the membrane, to drive motility, and to adhere to, pull on, and reorganize the extracellular matrix. Here I demonstrate that α-actinin-4, a well-known actin crosslinking protein and long believed to be the primary actin bundling protein for contractile actin arrays, actually inhibits bundling of actin filaments into stress fibers in epithelial cells. I show that α-actinin-4 accomplishes this by inhibiting tropomyosin dependent stabilization of filamentous actin, and maintains a dynamic basal actin array through promoting actin disassembly. Lastly I demonstrate that α-actinin-4 localization in cells can be modulated by phosphorylation of its actin-binding domain

Simultaneous Stretching and Contraction of Stress Fibers In Vivo

To study the dynamics of stress fiber components in cultured fibroblasts, we expressed α-actinin and the myosin II regulatory myosin light chain (MLC) as fusion proteins with green fluorescent protein. Myosin activation was stimulated by treatment with calyculin A, a serine/threonine phosphatase inhibitor that elevates MLC phosphorylation, or with LPA, another agent that ultimately stimulates phosphorylation of MLC via a RhoA-mediated pathway. The resulting contraction caused stress fiber shortening and allowed observation of changes in the spacing of stress fiber components. We have observed that stress fibers, unlike muscle myofibrils, do not contract uniformly along their lengths. Although peripheral regions shortened, more central regions stretched. We detected higher levels of MLC and phosphorylated MLC in the peripheral region of stress fibers. Fluorescence recovery after photobleaching revealed more rapid exchange of myosin and α-actinin in the middle of stress fibers, compared with the periphery. Surprisingly, the widths of the myosin and α-actinin bands in stress fibers also varied in different regions. In the periphery, the banding patterns for both proteins were shorter, whereas in central regions, where stretching occurred, the bands were wider

President\u27s Report and Honor Roll of Donors 2004-2005

Legacy of Distinction... Soaring to New Heightshttps://digitalcommons.bridgewater.edu/bridgewater_magazine/1118/thumbnail.jp

Actin based propulsion: Intriguing interplay between material properties and growth processes

Eukaryotic cells and intracellular pathogens such as bacteria or viruses utilize the actin polymerization machinery to propel themselves forward. Thereby, the onset of motion and choice of direction may be the result of a spontaneous symmetry-breaking or might be triggered by external signals and preexisting asymmetries, e.g. through a previous septation in bacteria. Although very complex, a key feature of cellular motility is the ability of actin to form dense polymeric networks, whose microstructure is tightly regulated by the cell. These polar actin networks produce the forces necessary for propulsion but may also be at the origin of a spontaneous symmetry-breaking. Understanding the exact role of actin dynamics in cell motility requires multiscale approaches which capture at the same time the polymer network structure and dynamics on the scale of a few nanometers and the macroscopic distribution of elastic stresses on the scale of the whole cell. In this chapter we review a selection of theories on how mechanical material properties and growth processes interact to induce the onset of actin based motion.Comment: 16 pages, 14 figures, chapter in book "Cell mechanics: from single scale-based models to multiscale modelling

COLLECTION 0032: David William Faupel Collection, 1859-2004

This archival collection contains correspondence, research notes, subject files, tracts, pamphlets and ephemera on the Pentecostal, Holiness and Keswick traditions, sermons, and reports. It also includes the personal biographical papers of David William Faupel. The Faupel book collection, separated to the Hubbard Library collections, contains many rare items documenting Pentecostalism in particular as well as America Evangelicalism in general

Funktionelle Analyse der atypischen Protein Kinase C

[no abstract

Investigations on the control of cell behaviour and the cell cycle

Little work has been done previously on cells grown as sail-sheets. This thesis describes the morphology, behaviour and movement of chick heart fibroblasts (CHFs) in sail-sheets and the effects of mechanical tension on actin content and the cell cycle of these cells. Abercrombie et ad. (1970 a) quantified the measurements on the features of movement of CHFs on glass coverslips (or, conventional cultures). Since the sail-sheet cultures appeared to resemble more closely the in vivo situation than the conventional cultures, it seemed appropriate that the features of cell movement in sail-sheets be studied and compared with those in conventional cultures. The work presented in this thesis suggests that CHFs in sail-sheets do exhibit such features as described for conventional cultures (Abercrombie et al., 1970 a) but at a relatively lower speed. Mechanical tension occurs within and between cells during embryogenesis, wound healing and in the repetitive contractile processes performed by various muscles of the body. Curtis and Seehar (1978) found that short-term tensing of sail-sheets with a low frequency oscillator shortened the duration of the cell cycle in CHFs. This thesis investigates whether tensing of sail-sheets for longer durations and at much lower frequencies produces any different effects than those found by Curtis and Seehar (1978). The work from these experiments suggested that on the whole, tension causes a reduction in the duration of the cell cycle. The effects of tension in a rectangular cell sheet differ from corners, edges and centres perhaps because of local stress concentration. The hypothesis that the effect of tension on the cell cycle may be due to its effect on the microfilaments was investigated. Results were inconclusive