Tensile force field plays a crucial role in local invasion of tumor cells through a mechano-chemical coupling mechanism.

Cancer metastasis starts from early local invasion, during which tumor cells detach from the primary tumor, penetrate the extracellular matrix (ECM), and then invade neighboring tissues. However, the cellular mechanics in the detaching and penetrating processes have not been fully understood, and the underlying mechanisms that influence cell polarization and migration in the 3D matrix during tumor invasion remain largely unknown. In this study, we employed a dual tumor-spheroid model to investigate the cellular mechanisms of the tumor invasion.

Circulating tumor cells with metastasis-initiating competence survive fluid shear stress during hematogenous dissemination through CXCR4-PI3K/AKT signaling.

To seed lethal secondary lesions, circulating tumor cells (CTCs) must survive all rate-limiting factors during hematogenous dissemination, including fluid shear stress (FSS) that poses a grand challenge to their survival. We thus hypothesized that CTCs with the ability to survive FSS in vasculature might hold metastasis-initiating competence. This study reported that FSS of physiologic magnitude selected a small subpopulation of suspended tumor cells in vitro with the traits of metastasis-initiating cells, including stemness, migration/invasion potential, cellular plasticity, and biophysical properties.

Neoteric Semiembedded β-Tricalcium Phosphate Promotes Osteogenic Differentiation of Mesenchymal Stem Cells under Cyclic Stretch.

β-Tricalcium phosphate (β-TCP) is a bioactive material for bone regeneration, but its brittleness limits its use as a standalone scaffold. Therefore, continuous efforts are necessary to effectively integrate β-TCP into polymers, facilitating a sturdy ion exchange for cell regulation. Herein, a novel semiembedded technique was utilized to anchor β-TCP nanoparticles onto the surface of the elastic polymer, followed by hydrophilic modification with the polymerization of dopamine.

Cell mechanics regulate the migration and invasion of hepatocellular carcinoma cells via JNK signaling.

Hepatocellular carcinoma (HCC) cells, especially those with metastatic competence, show reduced stiffness compared to the non-malignant counterparts. However, it is still unclear whether and how the mechanics of HCC cells influence their migration and invasion. This study reports that HCC cells with enhanced motility show reduced mechanical stiffness and cytoskeleton, suggesting the inverse correlation between cellular stiffness and motility.

Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.

Evidence from physical sciences in oncology increasingly suggests that the interplay between the biophysical tumor microenvironment and genetic regulation has significant impact on tumor progression. Especially, tumor cells and the associated stromal cells not only alter their own cytoskeleton and physical properties but also remodel the microenvironment with anomalous physical properties. Together, these altered mechano-omics of tumor tissues and their constituents fundamentally shift the mechanotransduction paradigms in tumorous and stromal cells and activate oncogenic signaling within the neoplastic niche to facilitate tumor progression.

The Mechanics of Tumor Cells Dictate Malignancy via Cytoskeleton-Mediated APC/Wnt/β-Catenin Signaling.

Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression, implicating the correlation between cell mechanics and malignancy. However, the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely understood. We report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in vivo.

Fluid shear stress enhances natural killer cell's cytotoxicity toward circulating tumor cells through NKG2D-mediated mechanosensing.

Tumor cells metastasize to distant organs mainly via hematogenous dissemination, in which circulating tumor cells (CTCs) are relatively vulnerable, and eliminating these cells has great potential to prevent metastasis. In vasculature, natural killer (NK) cells are the major effector lymphocytes for efficient killing of CTCs under fluid shear stress (FSS), which is an important mechanical cue in tumor metastasis. However, the influence of FSS on the cytotoxicity of NK cells against CTCs remains elusive.

Mechanical manipulation of cancer cell tumorigenicity via heat shock protein signaling.

Biophysical cues of rigid tumor matrix play a critical role in cancer cell malignancy. We report that stiffly confined cancer cells exhibit robust growth of spheroids in the stiff hydrogel that exerts substantial confining stress on the cells. The stressed condition activated Hsp (heat shock protein)-signal transducer and activator of transcription 3 signaling via the transient receptor potential vanilloid 4-phosphatidylinositol 3-kinase/Akt axis, thereby up-regulating the expression of the stemness-related markers in cancer cells, whereas these signaling activities were suppressed in cancer cells cultured in softer hydrogels or stiff hydrogels with stress relief or Hsp70 knockdown/inhibition.

Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential.

Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength.

Unraveling the mechanobiology of cornea: From bench side to the clinic.

The cornea is a transparent, dome-shaped structure on the front part of the eye that serves as a major optic element and a protector from the external environment. Recent evidence shows aberrant alterations of the corneal mechano-environment in development and progression of various corneal diseases. It is, thus, critical to understand how corneal cells sense and respond to mechanical signals in physiological and pathological conditions.

Biomechanics of cancer stem cells.

Cancer stem cells (CSCs) have been believed to be one driving force for tumor progression and drug resistance. Despite the significance of biochemical signaling in malignancy, highly malignant tumor cells or CSCs exhibit lower cellular stiffness than weakly malignant cells or non-CSCs, which are softer than their healthy counterparts, suggesting the inverse correlation between cell stiffness and malignancy. Recent years have witnessed the rapid accumulation of evidence illustrating the reciprocity between cell cytoskeleton/mechanics and CSC functions and the potential of cellular stiffness for specific targeting of CSCs.

Tumorigenic cell selection and substrate rigidity manipulation using 2D and 3D extracellular matrices.

Soft fibrin gels are used to select tumorigenic cells and regulate the stemness and metastasis of colorectal cancer cells via mechanotransduction. This protocol details steps to produce two-dimensional (2D) and three-dimensional (3D) extracellular matrices for substrate rigidity manipulation and tumorigenic cell selection. We also describe how it can be applied to tumor mechanotransductive research by colony growth monitoring and cell isolation.

Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion.

Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood.

Wavelength-regulated switchable photoelectrochemical system for concurrent detection of dual antibiotics.

Concurrent detection of antibiotics with high sensitivity and reliability is always of high importance for food safety and environmental monitoring. Herein, a wavelength-dependent photoelectrochemical (PEC) aptasensor based on TiO-Ag/nitrogen doped graphene composites (TiO-Ag/NDG) was developed for concurrent detection of two antibiotics with signal amplification function. The as-fabricated ternary nanocomposites could concurrently detect two antibiotics using two different aptamer molecules as recognition elements, amplify the photocurrent outputs and perform a photocurrent-switchable operation, where photocurrents could be switched between anodic direction and cathodic direction via simply regulating the irradiation wavelength.

Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold.

Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS.

Hybrid theranostic microbubbles for ultrasound/photoacoustic imaging guided starvation/low-temperature photothermal/hypoxia-activated synergistic cancer therapy.

Constructing a theranostic agent for high-contrast multimodality imaging-guided synergistic therapy with long-term tumor retention and minimum systemic side effects still remains a major challenge. Herein, a hybrid microbubble-based theranostic platform was developed for dual-modality ultrasound (US) and enhanced photoacoustic (PA) imaging-guided synergistic tumor therapy by combining starvation therapy, low-temperature photothermal therapy (PTT), and hypoxia-activated therapy, based on polydopamine (PDA) doped poly(vinyl alcohol) microbubbles loaded with glucose oxidase (GOx) (PDA-PVAMBs@GOx) and hypoxia-activated prodrug (HAP) tirapazamine (TPZ). For dual-modality US/enhanced PA imaging, PDA-PVAMBs provided 6.

Effects of Mechanical Compression on Cell Morphology and Function in Human Corneal Fibroblasts.

: To explore the effect of mechanical compression (similar to that induced by eye rubbing) on cell morphology, proliferation, apoptosis, and extracellular matrix synthesis and degradation in human corneal fibroblasts. Human corneal fibroblasts were isolated from corneal lenticule tissue of 10 patients after small incision lenticule extraction surgery. A system was established to mechanically compress corneal fibroblasts with pressure ranging from 0 to 524 Pa.

Biophysical properties of corneal cells reflect high myopia progression.

Myopia is a common ocular disorder with significant alterations in the anterior ocular structure, including the cornea. The cell biophysical phenotype has been proposed to reflect the state of various diseases. However, the biophysical properties of corneal cells have not been characterized during myopia progression and their relationship with myopia remains unknown.

Cell Cytoskeleton and Stiffness Are Mechanical Indicators of Organotropism in Breast Cancer.

Tumor metastasis involves the dissemination of tumor cells from the primary lesion to other organs and the subsequent formation of secondary tumors, which leads to the majority of cancer-related deaths. Clinical findings show that cancer cell dissemination is not random but exhibits organ preference or organotropism. While intrinsic biochemical factors of cancer cells have been extensively studied in organotropism, much less is known about the role of cell cytoskeleton and mechanics.

Manipulation of the Nanoscale Presentation of Integrin Ligand Produces Cancer Cells with Enhanced Stemness and Robust Tumorigenicity.

Developing strategies for efficient expansion of cancer stem-like cells (CSCs) will help investigate the mechanism underlying tumorigenesis and cancer recurrence. Herein, we report a dynamic culture substrate tethered with integrin ligand-bearing magnetic nanoparticles via a flexible polymeric linker to enable magnetic manipulation of the nanoscale ligand tether mobility. The cancer cells cultured on the substrate with high ligand tether mobility develop into large semispherical colonies with CSCs features, which can be abrogated by magnetically restricting the ligand tether mobility.