Mechanobiology in Medicine最新文献

Dendritic cells (DCs) play a pivotal role in bridging the innate and adaptive immune systems. From their immature state, scavenging tissue for foreign antigens to uptake, then maturation, to their trafficking to lymph nodes for antigen presentation, these cells are exposed to various forms of mechanical forces. Particularly, in the tumor microenvironment, it is widely known that microenvironmental biomechanical cues are heightened. The source of these forces arises from cell-to-extracellular matrix (ECM) and cell-to-cell interactions, as well as being exposed to increased microenvironmental pressures and fluid shear forces typical of tumors. DCs then integrate these forces, influencing their immune functions through mechanotransduction. This aspect of DC biology holds alternative, but important clues to understanding suppressed/altered DC responses in tumors, or allow the artificial enhancement of DCs for therapeutic purposes. This review discusses the current understanding of DC mechanobiology from the perspectives of DCs as sensors of mechanical forces and providers of mechanical forces.

Cellular behaviors such as migration, spreading, and differentiation arise from the interplay of cell–matrix interactions. The comprehension of this interplay has been advanced by the motor-clutch model, a theoretical framework that captures the binding-unbinding kinetics of mechanosensitive membrane-bound proteins involved in mechanochemical signaling, such as integrins. Since its introduction and subsequent development as a computational tool, the motor clutch model has been instrumental in elucidating the impact of biophysical factors on cellular mechanobiology. This review aims to provide a comprehensive overview of recent advances in the motor-clutch modeling framework, its role in elucidating the relationships between mechanical forces and cellular processes, and its potential applications in mechanomedicine.

Micropatterning is a sophisticated technique that precisely manipulates the spatial distribution of cell adhesion proteins on various substrates across multiple scales. This precise control over adhesive regions facilitates the manipulation of architectures and physical constraints for single or multiple cells. Furthermore, it allows for an in-depth analysis of how chemical and physical properties influence cellular functionality. In this comprehensive review, we explore the current understanding of the impact of geometrical confinement on cellular functions across various dimensions, emphasizing the benefits of micropatterning in addressing fundamental biological queries. We advocate that utilizing directed self-organization via physical confinement and morphogen gradients on micropatterned surfaces represents an innovative approach to generating functional tissue and controlling morphogenesis in vitro. Integrating this technique with cutting-edge technologies, micropatterning presents a significant potential to bridge a crucial knowledge gap in understanding core biological processes.

Bone adapts to mechanical loading by changing its shape and mass. Osteocytes, as major mechanosensors, are critical for bone modeling/remodeling in response to mechanical stimuli. Intracellular calcium oscillation is one of the early responses in osteocytes, and this further facilitates bone cell communication through released biochemical signals. Our previous study has found that mechanically induced calcium oscillations in osteocytes enhance the release of extracellular vesicles (EVs), and those released EVs can elevate bone formation activity. However, the mechanism of mechanically stimulated EVs’ regulation of bone formation and resorption is still unclear. Here, using in vitro studies, we exposed OCY454 cells, with relatively high sclerostin expression, to steady fluid flow (SFF) and characterized the functions of rapidly released EVs in osteoblast and osteoclast regulation. Our study demonstrates that SFF stimulates intracellular calcium response in OCY454 cells and further induces sclerostin, osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) inside or outside EVs to regulate osteoblast and osteoclast activities. This load-induced protein and EVs release is load-duration dependent. Moreover, stimulated osteocytes rapidly regulate osteoclast maturation through EVs capsulated RANKL. In contrast, other regulating proteins, OPG, and sclerostin, are mainly released directly into the medium without EV capsulation.

The significance of early detection and isolation of infected individuals, along with the quantitative assessment of antibodies against the virus, has gained widespread recognition during the ongoing covid-19 pandemic. This necessitates the development of cost-effective, user-friendly, decentralized testing methods characterized by both high sensitivity and specificity. In this article, we present a comprehensive review of an innovative, low-cost rapid decentralized immunoassay technology, applicable across various diagnostic and quantitative testing scenarios. Distinguishing itself from conventional immunoassay technologies, this method is featured with mechanically enhanced specificity without compromising sensitivity. We delve into the basic principle of the technology and a comparative analysis of this technology in relation to other immunodiagnostic methods, highlighting its potential applications in a wide spectrum of diagnostic tests.

The dynamic protrusions of lamellipodia and filopodia have emerged as crucial players in tumor progression and metastasis. These membrane structures, governed by intricate actin cytoskeletal rearrangements, facilitate cancer cell migration, invasion, and interaction with the tumor microenvironment. This review provides a comprehensive examination of the structural and functional attributes of lamellipodia and filopodia, shedding light on their pivotal roles in mediating cancer invasion. Navigating through the intricate landscape of cancer biology, the review illuminates the intricate signaling pathways and regulatory mechanisms orchestrating the formation and activity of these protrusions. The discussion extends to the clinical implications of lamellipodia and filopodia, exploring their potential as diagnostic and prognostic markers, and delving into therapeutic strategies that target these structures to impede cancer progression. As we delve into the future, the review outlines emerging technologies and unexplored facets that beckon further research, emphasizing the need for collaborative efforts to unravel the complexities of lamellipodia and filopodia in cancer, ultimately paving the way for innovative therapeutic interventions.

Distal metastasis is the main cause of clinical treatment failure in patients with colon cancer. It is now known that the invasion and metastasis of cancer cells is precisely regulated by chemical and physical factors in vivo. However, the role of extracellular matrix (ECM) stiffness in colon cancer cell (CCCs) invasion and metastasis remains unclear. Here, bioinformatical analysis suggested that a high expression level of yes associated protein 1 (YAP1) was significantly associated with metastasis and poor prognosis in colon cancer patients. We further investigated the effects of polyacrylamide hydrogels with different stiffnesses (3, 20, and 38 ​kPa), which were simulated as ECM, on the mechanophenotype (F-actin cytoskeleton organization, electrophoretic rate, membrane fluidity, and Young's modulus) of CCCs. The results showed that a stiffer ECM could induce the maturation of focal adhesions and formation of stress fibers in CCCs, regulate their mechanophenotypes, and promote cell motility. We also demonstrated that the expression levels of YAP1 and paxillin were positively correlated in patients with colon cancer. YAP1 knockdown reduces paxillin clustering and cell motility and alters the cellular mechanophenotypes of CCCs. This is of great significance for an in-depth understanding of the invasion and metastatic mechanisms of colon cancer and for the optimization of clinical therapy from the perspective of mechanobiology.

Multiplex ultrasensitive detection of low abundance proteins remains a significant challenge in clinical applications, necessitating the development of innovative solutions. The integration of bead-based microfluidic chip platforms with their efficient target capture and separation capabilities, along with the advantages of miniaturization and low reagent consumption, holds great promise for building an integrated point-of-care testing (POCT) system that enables seamless sample input-result output. This review presents a comprehensive overview of recent advancements in bead-based microfluidic platforms for multiplex and ultrasensitive immunoassays, along with their potential applications in clinical diagnosis and treatment, which is organized into four sections: encoding techniques, the role of microfluidic platforms, applications, and future prospects.

A recent study published in Nature Communications showed that essential modulatory roles of interfacial adhesion and mechanical microenvironments such as geometric constraints and extracellular matrix stiffness, in microbe-host cell interactions. This study utilized single-cell force spectroscopy and RNA sequencing to gain insight into the intrinsic mechanisms by which the mechanical microenvironment regulates bacterial-host interactions and therefore reveal potential interventions against bacterial invasion. Meanwhile, the adhesion forces involved in the bacterial–host interactions were recognized as a new indicator for assessing the extent of bacterial infection. Taken together, these findings demonstrate that interfacial adhesion forces and mechanical microenvironments play a dominant role in modulating functions and behaviors of microorganisms and host cells, which also provide a mechanobiology-inspired idea for the development of subsequent drug-resistant antimicrobials and broad-spectrum antiviral drugs.

A recent study published in Nature Communications demonstrated that restoring SERCA2 pump deficiency can enhance bone mechano-responsiveness in type 2 diabetes (T2D) by modulating osteocyte calcium dynamics. The findings revealed that in T2D mice, the ability of the bone to respond to mechanical stress is compromised, primarily due to attenuated calcium oscillatory dynamics within osteocytes rather than in osteoblasts or osteoclasts. The underlying mechanism of this reduction in bone mechano-responsiveness in T2D was identified as a specific decrease in osteocytic SERCA2 expression mediated by PPARα. Additionally, mice overexpressing SERCA2 in osteocytes exhibited reduced deterioration of bone mechano-responsiveness induced by T2D. Collectively, this study provides mechanistic insights into T2D-induced deterioration in bone mechano-responsiveness and identifies a promising therapeutic approach to counteract T2D-associated fragility fractures.