Mechanobiology in Medicine最新文献

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.

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.