Mechanobiology in Medicine最新文献

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.

Bone and immune cells typically inhabit the same microenvironment and engage in mutual interactions to collectively execute the functions of the “osteoimmune system.” Establishing a harmonized and enduring osteoimmune system significantly enhances bone regeneration, necessitating the maintenance of bone and immune homeostasis. Recently, mechanobiology has garnered increasing interest in bone tissue engineering, with matrix stiffness emerging as a crucial parameter that has been extensively investigated. The effect of matrix stiffness on bone homeostasis remains relatively clear. Soft substrates tend to significantly affect the chondrogenic differentiation of bone marrow mesenchymal stem cells, whereas increasing matrix stiffness is advantageous for osteogenic differentiation. Increased stiffness increases osteoclast differentiation and activity. Additionally, there is increasing emphasis on immune homeostasis, which necessitates dynamic communication between immune cells. Immune cells are crucial in initiating bone regeneration and driving early inflammatory responses. Functional changes induced by matrix stiffness are pivotal for determining the outcomes of engineered tissue mimics. However, inconsistent and incomparable findings regarding the responses of different immune cells to matrix stiffness can be perplexing owing to variations in the stiffness range, measurement methods, and other factors. Therefore, this study aimed to provide a comprehensive review of the specific effects of matrix stiffness on diverse immune cells, with a particular focus on its implications for bone regeneration, which would offer theoretical insights into the treatment of large segmental bony defects and assist in the clinical development of new engineering strategies.

The gastrointestinal (GI) tract's primary role is food digestion, relying on coordinated fluid secretion and bowel movements triggered by mechanosensation. Enteroendocrine cells (EECs) are specialized mechanosensitive cells that convert mechanical forces into electrochemical signals, culminating in serotonin release to regulate GI motility. Despite their pivotal role, knowledge of EEC mechanical properties has been lacking due to their rarity and limited accessibility. In this brief report, we present the first single-cell mechanical characterization of human ECCs isolated from healthy intestinal organoids. Using single-cell optical tweezers, we measured EEC stiffness profiles at the physiological temperature and investigated changes following tryptophan metabolism inhibition. Our findings not only shed light on EEC mechanics but also highlight the potential of adult stem cell-derived organoids for studying these elusive cells.

Mechanotransduction is essential for cell fate and behavior, and F-actin plays a key role in the generation and transmission of molecular forces. A recent study published in Nature Communication presented a novel high-precision molecular tension measurement method using a Förster resonance energy transfer–based tension sensor with separated load-bearing function within distinct F-actin structures, and demonstrated that cellular mechanical anisotropy depends on cell shape, loading direction, and magnitude.

Osteoarthritis (OA) is a progressive degenerative joint sickness related with mechanics, obesity, ageing, etc., mainly characterized by cartilage degeneration, subchondral bone damage and synovium inflammation. Coordinated mechanical absorption and conduction of the joint play significant roles in the prevalence and development of OA. Subchondral bone is generally considered a load-burdening tissue where mechanosensitive cells are resident, including osteocytes, osteoblast lineage cells, and osteoclast lineage cells (especially less concerned in mechanical studies). Mechano-signaling imbalances affect complicated cellular events and disorders of subchondral bone homeostasis. This paper will focus on the significance of mechanical force as the pathogenesis, involvement of various mechanical force patterns in mechanosensitive cells, and mechanobiology research of loading devices in vitro and in vivo, which are further discussed. Additionally, various mechanosensing structures (e.g., transient receptor potential channels, gap junctions, primary cilia, podosome-associated complexes, extracellular vesicles) and mechanotransduction signaling pathways (e.g., Ca²⁺ signaling, Wnt/β-catenin, RhoA GTPase, focal adhesion kinase, cotranscriptional activators YAP/TAZ) in mechanosensitive bone cells. Finally, we highlight potential targets for improving mechanoprotection in the treatment of OA. These advances furnish an integration of mechanical regulation of subchondral bone homeostasis, as well as OA therapeutic approaches by modulating mechanical homeostasis.

A recent study published in Nature Communications introduces a novel mechanically-mediated reaction involving ZnO nanoparticles that autonomously react, forming Zn/S mineral microrods within an organogel. These microrods selectively reinforce synthetic polymer composites, offering a unique approach to material strengthening. The method provides a distinctive pathway for mechanical mineralization in composite materials.

Type 1 hypersensitivity involves an exaggerated immune reaction triggered by allergen exposure, leading to rapid release of inflammatory mediators. Meanwhile, mechanobiology explores how physical forces influence cellular processes, and recent research underscores its relevance in allergic reactions. This review provides a concise overview of Type 1 hypersensitivity, highlighting the pivotal role of mast cells and immunoglobulin E (IgE) antibodies in orchestrating allergic reactions. Recognizing the dynamic nature of cellular responses in allergies, this study subsequently delves into the emerging field of mechanobiology and its significance in understanding the mechanical forces governing immune cell behavior. Furthermore, molecular forces during mast cell activation and degranulation are explored, elucidating the mechanical aspects of IgE binding and cytoskeletal rearrangements. Next, we discuss the intricate interplay between immune cells and the extracellular matrix, emphasizing the impact of matrix stiffness on cellular responses. Additionally, we examine key mechanosensitive signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, Rho guanosine triphosphatase (GTPase) and integrin-mediated focal adhesion signaling, shedding light on their contributions to hypersensitivity reactions. This interplay of mechanobiology and Type 1 hypersensitivity provides insights into potential therapeutic targets and biomarkers, paving the way for better clinical management of Type 1 hypersensitivity reactions.

Mechanical models offer a quantitative framework for understanding scientific problems, predicting novel phenomena, and guiding experimental designs. Over the past few decades, the emerging field of cellular mechanobiology has greatly benefited from the substantial contributions of new theoretical tools grounded in mechanical models. Within the expansive realm of mechanobiology, the investigation of how cells sense and respond to their microenvironment has become a prominent research focus. There is a growing acknowledgment that cells mechanically interact with their external surroundings through an integrated machinery encompassing the cell membrane, cytoskeleton, and nucleus. This review provides a comprehensive overview of mechanical models addressing three pivotal components crucial for force transmission within cells, extending from mechanosensitive receptors on the cell membrane to the actomyosin cytoskeleton and ultimately to the nucleus. We present the existing numerical relationships that form the basis for understanding the structures, mechanical properties, and functions of these components. Additionally, we underscore the significance of developing mechanical models in advancing cellular mechanobiology and propose potential directions for the evolution of these models.

Neural stem cells in vivo receive information from biochemical and biophysical cues of their microenvironment that affect their survival, proliferation and differentiation toward specific lineages. Recapitulation of these conditions in vitro is better achieved in 3D cell cultures. Especially the cells that grow in scaffold-dependent 3D cultures establish more complex cell–cell and cell–material interactions enabling the study of the various signaling pathways. The biochemical signaling from growth factors and hormones has been extensively studied over the years. More recently cumulative evidence demonstrates that cell sensing and response to mechanical stimuli is mediated through mechanotransduction pathways. Although individual signaling pathways activated by biochemical or mechanical cues in cells are well-studied, synergistic or antagonistic effects among them need further research to be fully understood. The understanding of the alteration of the cell behavior due to a microenvironmental cues would be greatly enhanced by the study of key elements that lie in the convergence of biochemical and mechanical pathways. Here we analyzed the effect of the substrate topography on the nerve growth factor (NGF) induced differentiation of PC12 cells. Our results showed that the topography interferes with NGF-induced neuronal differentiation and this is reflected in the reduced activation of the integrin-mediated mechanotransduction.