Magnetic-programmable organohydrogels with reconfigurable network for mechanical homeostasis

Nano Research ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 255-259
Author(s):  
Yingchao Yang ◽  
Qian Liu ◽  
Tianyi Zhao ◽  
Yunfei Ru ◽  
Ruochen Fang ◽  
...  
Author(s):  
Jonas F. Eichinger ◽  
Maximilian J. Grill ◽  
Iman Davoodi Kermani ◽  
Roland C. Aydin ◽  
Wolfgang A. Wall ◽  
...  

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.


2021 ◽  
Vol 22 (23) ◽  
pp. 12928
Author(s):  
Constança Júnior ◽  
Maria Narciso ◽  
Esther Marhuenda ◽  
Isaac Almendros ◽  
Ramon Farré ◽  
...  

Pulmonary fibrosis (PF) is a progressive disease that disrupts the mechanical homeostasis of the lung extracellular matrix (ECM). These effects are particularly relevant in the lung context, given the dynamic nature of cyclic stretch that the ECM is continuously subjected to during breathing. This work uses an in vivo model of pulmonary fibrosis to characterize the macro- and micromechanical properties of lung ECM subjected to stretch. To that aim, we have compared the micromechanical properties of fibrotic ECM in baseline and under stretch conditions, using a novel combination of Atomic Force Microscopy (AFM) and a stretchable membrane-based chip. At the macroscale, fibrotic ECM displayed strain-hardening, with a stiffness one order of magnitude higher than its healthy counterpart. Conversely, at the microscale, we found a switch in the stretch-induced mechanical behaviour of the lung ECM from strain-hardening at physiological ECM stiffnesses to strain-softening at fibrotic ECM stiffnesses. Similarly, we observed solidification of healthy ECM versus fluidization of fibrotic ECM in response to stretch. Our results suggest that the mechanical behaviour of fibrotic ECM under stretch involves a potential built-in mechanotransduction mechanism that may slow down the progression of PF by steering resident fibroblasts away from a pro-fibrotic profile.


Author(s):  
Marcos Latorre ◽  
Bart Spronck ◽  
Jay D. Humphrey

Arteries are exposed to relentless pulsatile haemodynamic loads, but via mechanical homeostasis they tend to maintain near optimal structure, properties and function over long periods in maturity in health. Numerous insults can compromise such homeostatic tendencies, however, resulting in maladaptations or disease. Chronic inflammation can be counted among the detrimental insults experienced by arteries, yet inflammation can also play important homeostatic roles. In this paper, we present a new theoretical model of complementary mechanobiological and immunobiological control of vascular geometry and composition, and thus properties and function. We motivate and illustrate the model using data for aortic remodelling in a common mouse model of induced hypertension. Predictions match the available data well, noting a need for increased data for further parameter refinement. The overall approach and conclusions are general, however, and help to unify two previously disparate literatures, thus leading to deeper insight into the separate and overlapping roles of mechanobiology and immunobiology in vascular health and disease.


Author(s):  
Peter Nietmann ◽  
Jonathan E.F. Bodenschatz ◽  
Andrea M. Cordes ◽  
Jannis Gottwald ◽  
Helen Rother-Nöding ◽  
...  

2020 ◽  
Vol 117 (41) ◽  
pp. 25532-25542 ◽  
Author(s):  
Jonathan D. Winkelman ◽  
Caitlin A. Anderson ◽  
Cristian Suarez ◽  
David R. Kovar ◽  
Margaret L. Gardel

The actin cytoskeleton assembles into diverse load-bearing networks, including stress fibers (SFs), muscle sarcomeres, and the cytokinetic ring to both generate and sense mechanical forces. The LIM (Lin11, Isl- 1, and Mec-3) domain family is functionally diverse, but most members can associate with the actin cytoskeleton with apparent force sensitivity. Zyxin rapidly localizes via its LIM domains to failing SFs in cells, known as strain sites, to initiate SF repair and maintain mechanical homeostasis. The mechanism by which these LIM domains associate with stress fiber strain sites (SFSS) is not known. Additionally, it is unknown how widespread strain sensing is within the LIM protein family. We identify that the LIM domain-containing region of 18 proteins from the Zyxin, Paxillin, Tes, and Enigma proteins accumulate to SFSS. Moreover, the LIM domain region from the fission yeast protein paxillin like 1 (Pxl1) also localizes to SFSS in mammalian cells, suggesting that the strain sensing mechanism is ancient and highly conserved. We then used sequence and domain analysis to demonstrate that tandem LIM domains contribute additively, for SFSS localization. Employing in vitro reconstitution, we show that the LIM domain-containing region from mammalian zyxin and fission yeast Pxl1 binds to mechanically stressed F-actin networks but does not associate with relaxed actin filaments. We propose that tandem LIM domains recognize an F-actin conformation that is rare in the relaxed state but is enriched in the presence of mechanical stress.


2006 ◽  
Vol 3 (11) ◽  
pp. 719-740 ◽  
Author(s):  
Ghassan S Kassab

Biomechanics relates the function of a physiological system to its structure. The objective of biomechanics is to deduce the function of a system from its geometry, material properties and boundary conditions based on the balance laws of mechanics (e.g. conservation of mass, momentum and energy). In the present review, we shall outline the general approach of biomechanics. As this is an enormously broad field, we shall consider a detailed biomechanical analysis of the aorta as an illustration. Specifically, we will consider the geometry and material properties of the aorta in conjunction with appropriate boundary conditions to formulate and solve several well-posed boundary value problems. Among other issues, we shall consider the effect of longitudinal pre-stretch and surrounding tissue on the mechanical status of the vessel wall. The solutions of the boundary value problems predict the presence of mechanical homeostasis in the vessel wall. The implications of mechanical homeostasis on growth, remodelling and postnatal development of the aorta are considered.


2019 ◽  
Author(s):  
Susanne Karsch ◽  
Fanny Büchau ◽  
Thomas M. Magin ◽  
Andreas Janshoff

AbstractThe isotype-specific composition of the keratin cytoskeleton is important for strong adhesion, force resilience, and barrier function of the epidermis. However, the mechanisms by which keratins regulate these functions are still incompletely understood. In this study, the role and significance of the keratin network for mechanical integrity, force transmission, and barrier formation were analyzed in murine keratinocytes. Following the time-course of single-cell wounding, wildtype (WT) cells slowly closed the gap in a collective fashion involving tightly connected neighboring cells. In contrast, the mechanical response of neighboring cells was compromised in keratin-deficient cells, causing an increased wound area initially and an inefficient overall wound closure. Furthermore, the loss of the keratin network led to impaired, fragmented cell-cell junctions and triggered a profound change in the overall cellular actomyosin architecture. Electrical cell-substrate impedance sensing of cell junctions revealed a dysfunctional barrier in knockout (Kty−/−) compared to WT cells. These findings demonstrate that Kty−/− cells display a novel phenotype characterized by loss of mechanocoupling and failure to form a functional barrier. Re-expression of K5/K14 rescued the barrier defect to a significant extent and reestablished the mechanocoupling with remaining discrepancies likely due to the low abundance of keratins in that setting. Our study reveals the major role of the keratin network for mechanical homeostasis and barrier functionality in keratinocyte layers.


2017 ◽  
Vol 17 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Lüwen Zhou ◽  
Chen Zhang ◽  
Fan Zhang ◽  
Shouqin Lü ◽  
Shujin Sun ◽  
...  

2012 ◽  
Vol 135 (1) ◽  
Author(s):  
Patrick M. McGah ◽  
Daniel F. Leotta ◽  
Kirk W. Beach ◽  
R. Eugene Zierler ◽  
Alberto Aliseda

Arteriovenous fistulae are surgically created to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is, in part, a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. We present computational hemodynamic simulations in four patient-specific models of mature arteriovenous fistulae reconstructed from 3D ultrasound scans. Our results suggest that these mature fistulae have remodeled to return to ‘‘normal’’ shear stresses away from the anastomoses: about 1.0 Pa in the outflow veins and about 2.5 Pa in the inflow arteries. Large parts of the anastomoses were found to be under very high shear stresses >15 Pa, over most of the cardiac cycle. These results suggest that the remodeling process works toward restoring mechanical homeostasis in the fistulae, but that the process is limited or incomplete, even in mature fistulae, as evidenced by the elevated shear at or near the anastomoses. Based on the long term clinical viability of these dialysis accesses, we hypothesize that the elevated nonhomeostatic shear stresses in some portions of the vessels were not detrimental to fistula patency.


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