Mechanobiology in Medicine最新文献

The mechanical microenvironment strongly affects cell state and decisions. Cell mechanosensing has been described by a molecular clutch which gets progressively engaged depending upon the stiffness of the extracellular material. Through the actuation of pulling forces exerted by actin fibres on the mechanosensitive talin-integrin molecular complex, cells sense and react to the stiffness of their surroundings. However, whether the truly cell mechanosensing is regulated by the pure elastic stiffness or by the strain energy density of the ECM is still debated. Here we report that the cell response to change of strain energy density out of loading induced deformation (purely elastic) can be accounted for by including, within the same frame of the molecular clutch model, the residual strain/stress to which the ECM could be subjected before establishing any interaction with the molecular clutches. To include the contribution of residual stresses, an additional spring orthogonal to the ones already present in the original clutch model has been introduced; this spring takes memory of the ECM strain energy when axially deformed before any interaction with cell molecular clutches can occur. To evaluate the influence of strain on the optimum number of clutches, the model has been implemented with different levels of strain. Results suggest that cells undergo a reinforcement process, stiffening the cytoskeleton in response to the ECM stress/strain energy.

Covalent organic frameworks (COFs) are emerging crystalline porous materials composed of covalently linked and periodically arranged organic molecules, which exhibit mechanical properties mediated by structural diversity. Meanwhile, the tunable mechanical properties of COFs have been widely applied in drug delivery and cancer therapy. Herein, we first summarize the regulation strategies of COFs with different mechanical strengths, such as structural dimensions, pore sizes, and host–guest interaction forces. Then, the remarkable achievements of COFs with different mechanical properties in drug delivery and cancer therapy in recent years are introduced. Finally, the mechanical strength regulation of COFs and the remaining challenges for biomedical applications are presented. This review provides a more comprehensive understanding of the application of COFs systems with tunable mechanical properties in the field of biomedicine, and promotes the development of interdisciplinary research between COFs materials and nanomedicine.

A recent study published in Cell Stem Cell [1] showed that matrix stiffness critically regulates hematopoietic stem cell (HSC) niche, and successfully engineered a soft bone marrow (BM) organoid to maintain and rejuvenate HSCs ex vivo. In addition, BM stiffening was also identified as a novel aging hallmark of the hematopoietic system. Together, these important findings implicate matrix stiffness as a fundamental biomechanical factor governing cell fate determination and aging of tissue-specific stem cells.

We have shown that platelet-derived microvesicles (PMVs) induce abnormal proliferation, migration, and energy metabolism of vascular smooth muscle cells (VSMCs) after vascular intimal injury. Here, we examined a novel role of podosome in mediating matrix metalloproteinase-9 (MMP-9) dependent VSMC migration induced by platelet-derived microvesicles (PMVs). VSMCs were isolated from the thoracic aortas of male Sprague Dawley (SD) rats and identified with immunofluorescent staining. Blood samples were collected from SD Rats, the platelets were isolated with density gradient centrifugation from the blood samples and activated by collagen I. Intriguingly, proteins expressed in platelets were found to participate in the positive regulation of podosome assembly using GO analysis by DAVID, and most of the proteins were found in extracellular exosomes. Of note, activated platelets indirectly induced VSMC migration via releasing PMVs which was verified using platelets and VSMCs transwell co-culture system. Besides, podosome, an invasive protrusion to mediate extracellular matrix (ECM) remodeling, was formed in VSMCs to induce cell migration. Furthermore, MMP-9 activity detected by gelatin zymography was used to verify the function of the podosome in ECM remodeling. The result indicated that MMP-9 activity was robustly activated in VSMCs to implement the function of the podosome. In addition, gelatin degradation was detected in intact VSMCs using a gelatin degradation assay after co-culture with platelets. Taken together, our data reveal a novel mechanism that PMVs promote VSMC migration via forming podosomes and inducing MMP-9 activity.

Anisodamine and anisodine have been used in treatment of septic shock, but the underlying mechanism are still unclear. In the present study, the effects of anisodamine hydrobromide (Ani HBr) and anisodine hydrobromide (AT3) on the mesenteric hemodynamics in septic shock rats were performed. The rat model of septic shock was established by intravenous tail vein injection of 5 ​mg/kg lipopolysaccharide (LPS), and then treated with Ani HBr, AT3, racemic anisodine (Race Ani) or atropine (ATP). The mesenteric microcirculation was observed using the intravital microscopy. Then, the flow pattern of the microcirculation, leukocytes dynamics and the plasma levels of cytokines tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were analyzed. Compared with the control rats, reduced mean arterial pressure, increased heart rate, and slow microcirculatory blood flow was found in septic shock rats. The main abnormal flow patterns were intermittent and reciprocating motions. Ani HBr, AT3, Race Ani and ATP elevated the mean arterial pressure and reduced heart rate in septic shock rats. Ani HBr and AT3 not only restored the velocity of microcirculatory blood flow and improved the microcirculatory flow patterns, but also suppressed the LPS-induced leukocyte-endothelium interaction and releases of TNF-α and IL-6. Therefore, Ani HBr and AT3 improves hemodynamics in both macro- and microcirculation, which provide a novel experimental basis for exploring the mechanobiological mechanisms in septic shock.

Mechanotransduction, the transfer of mechanical stimuli into various biological signals, is a vital biological process in multiple organ systems. The osteoclast (OC) plays a vital role in bone metabolism and repair. The role of mechanotransduction in osteoclasts and other bone cells is emerging. This commentary highlights a recent research report on a novel strategy for the precise regulation of OC formation via modulating matrix stiffness. Modulation of the mechanotransduction pathways in the skeletal system will pave the way for the development of a matrix stiffness-based strategy for bone tissue regeneration.

Mechanobiology is the study of how mechanical forces affect biological systems, including cells and tissues. The two-photon lithography (TPL) as a powerful 3D printing technique allows the creation of 3D complex structures at a microscopic scale. By applying the TPL into the mechanobiology studies, researchers could create precise structures that mimic the mechanical properties of biological system, allowing for the study of mechanobiological processes in a controlled environment. This implies applications in tissue engineering, drug screening, and fundamental research into the mechanisms of mechanobiology. In this review, we highlight recent advances in TPL for mechanobiology studies, as well as the potential future directions for this promising field.

Mechanobiology is an interdisciplinary discipline combining biology, engineering, chemistry, physics, and medicine. Mechanobiology research comprehensively discusses, the role of mechanical factors in various life processes and the occurrence and development of associated and diseases at the whole organism, organ, cell, protein and gene levels. The cellular and molecular mechanisms of mechanical signal transduction and response are elucidated, in addition to the discovery of novel biomarkers and potential drug targets, which are mechanosensitive molecules. This paper reviews the development of mechanobiology research in China since the new century, while focusing on the research achievements of Chinese scientists in the field of mechanobiology over the last three years, including cardiovascular, bone and joint, tumor, cellular, and molecular mechanobiology. Meanwhile, it has been suggested that in the future, mechanobiology research should include are indicated detailed studies on the mechanobiological mechanism of diseases at the cellular and molecular levels firstly, so that the newly discovered biomarkers or potential targets can gradually achieve clinical transformation. Second, future research should strengthen the qualitative and quantitative combination of biological experiments and mechanical and mathematical modeling analyses, especially at cellular, subcellular and molecular scales. Mechanobiological studies are of great theoretical and practical significance for our understanding of the mechanical mechanisms and natural laws of growth and senility of the human body, expounding pathological mechanisms of diseases, and researching and developing new medicines and technologies to promote biomedical and clinical research for human health.

Dysfunctions of calcium cycling occur in heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). HFrEF and HFpEF showed Ca²⁺ leakage at diastole. The compensation of Na⁺/Ca²⁺ exchanger and the decrease of T-tubule density reduces cytoplasmic Ca²⁺ concentration in HFrEF and impairs systolic function. In contrast, HFpEF has the increase of cytoplasmic Ca²⁺ concentration and diastolic dysfunctions. The decrease of mitochondrial Ca²⁺ concentration weakens myocardial contractility in HFrEF while the increased concentration retains the contractility in HFpEF. Here, the changes of calcium cycling in HFrEF and HFpEF are summarized and the possibility of relevant therapeutic targets is discussed.