Mechanobiology in Medicine最新文献

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.

Accumulating evidence strongly suggests that cell chirality plays a pivotal role in driving left-right (LR) symmetry breaking, a widespread phenomenon in living organisms. Whole embryos and excised organs have historically been employed to investigate LR symmetry breaking and have yielded exciting findings. In recent years, in vitro engineered platforms have emerged as powerful tools to reveal cellular chiral biases and led to uncovering molecular and biophysical insights into chiral morphogenesis, including the significant role of the actin cytoskeleton. Establishing a link between observed in vivo tissue chiral morphogenesis and the determined chiral bias of cells in vitro has become increasingly important. In this regard, computational mathematical models hold immense value as they can explain and predict tissue morphogenic behavior based on the chiral biases of individual cells. Here, we present the formulations and discoveries achieved using various computational models spanning different biological scales, from the molecular and cellular levels to tissue and organ levels. Furthermore, we offer insights into future directions and the role of such models in advancing the study of asymmetric cellular mechanobiology.

Radiation therapy is one of the most effective therapeutic modalities for tumors. The changes in matrix stiffness of tumors and associated tissues are important consequences of side effects after radiotherapy. They are documented to induce the radio-resistance of cancer cells and promote the recurrence and metastasis of tumors, resulting in poor patient prognosis. Identifying the relationship between radiation and matrix stiffness is beneficial to optimize clinical treatment schemes and ultimately improve the patient prognosis. Herein, this review includes knowledge regarding the specific cellular, molecular processes and relevant clinical factors of the changes in matrix stiffness of tumors or associated tissues induced by radiation. The effects of altered matrix stiffness on the behaviors of cancer cells and associated normal cells are further detailed. It also reviews literatures to elucidate the mechanical signal transduction mechanism in radiotherapy and proposes some strategies to enhance the efficacy of radiotherapy based on matrix mechanics.

A recent study published in Nature Communications presents a unique approach using an osteoinductive intramedullary (IM) implant as an adjunctive therapy for bone transport distraction osteogenesis. The study demonstrates that this innovative technique achieves early bony bridging, eliminates pin tract infections, and prevents docking site non-union, offering significant potential for the treatment of large bone defects. The study also highlights an additive effect of the osteoinductive IM implant on distraction osteogenesis for managing bone defect.

A recent study published in Science Advances¹ showed the influence of Yap on notochord formation and NT (neural tube) patterning in vertebrate embryonic development, and conducted an in-depth study from the perspective of biomechanical signal mechanotransduction. In addition, this study also explored the possible complex interaction between mechanical signals and gene expression. Together, this study provides new insights into the development mechanism of early vertebrate embryos.

The implantation of foreign materials often leads to fibroblast activation and fibrous capsule formation. The process of fibroblast-to-myofibroblast transition (FMT) is partially influenced by the surface properties of biomaterials, including factors such as stiffness, wettability, roughness, and topography. This article reviews the studies that concentrate on the connection between the topographical cues of biomaterials and FMT. We have summarized the key findings and subsequently analyzed the potential reasons behind the contradictory conclusions in these studies.

The mechanical constraints in the overcrowding glioblastoma (GBM) microenvironment have been implicated in the regulation of tumor heterogeneity and disease progression. Especially, such mechanical cues can alter cellular DNA transcription and give rise to a subpopulation of tumor cells called cancer stem cells (CSCs). These CSCs with stem-like properties are critical drivers of tumorigenesis, metastasis, and treatment resistance. Yet, the biophysical and molecular machinery underlying the emergence of CSCs in tumor remained unexplored. This work employed a two-dimensional micropatterned multicellular model to examine the impact of mechanical constraints arisen from geometric confinement on the emergence and spatial patterning of CSCs in GBM tumor. Our study identified distinct spatial distributions of GBM CSCs in different geometric patterns, where CSCs mostly emerged in the peripheral regions. The spatial pattern of CSCs was found to correspond to the gradients of mechanical stresses resulted from the interplay between the cell-ECM and cell–cell interactions within the confined environment. Further mechanistic study highlighted a Piezo1-RhoA-focal adhesion signaling axis in regulating GBM cell mechanosensing and the subsequent CSC phenotypic transformation. These findings provide new insights into the biophysical origin of the unique spatial pattern of CSCs in GBM tumor and offer potential avenues for targeted therapeutic interventions.