Aims: CAR-T cell therapy has attracted considerable attention in recent years owing to its well-known efficacy against haematopoietic malignancies. Nevertheless, this immunotherapy fails against solid tumours due to hostile conditions found in the tumour microenvironment. In this context, many relevant biochemical factors have been thoroughly studied, but crucial mechanical cues have been underestimated.
View Article and Find Full Text PDFMechanical signals are crucial in regulating the response of cells in a monolayer to both physiological and pathological stressors, including intracellular bacterial infections. In particular, during intracellular infection of epithelial cells in monolayer with the food-borne bacterial pathogen Listeria monocytogenes, cellular biomechanics dictates the degree of bacterial dissemination across the monolayer. This occurs through a process whereby surrounder uninfected cells mechanically compete and eventually extrude infected cells.
View Article and Find Full Text PDFProstate cancer (PCa) is a major world-wide health concern. Current diagnostic methods involve Prostate-Specific Antigen (PSA) blood tests, biopsies, and Magnetic Resonance Imaging (MRI) to assess cancer aggressiveness and guide treatment decisions. MRI aligns with medicine, as patient-specific image biomarkers can be obtained, contributing towards the development of digital twins for clinical practice.
View Article and Find Full Text PDFThe nucleus of eukaryotic cells is constantly subjected to different kinds of mechanical stimuli, which can impact the organization of chromatin and, subsequently, the expression of genetic information. Experiments from different groups showed that nuclear deformation can lead to transient or permanent condensation or decondensation of chromatin and the mechanical activation of genes, thus altering the transcription of proteins. Changes in chromatin organization, in turn, change the mechanical properties of the nucleus, possibly leading to an auxetic behavior.
View Article and Find Full Text PDFBackground And Objective: Immune cell migration is one of the key features that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors. Chimeric antigen receptor (CAR) T-cell therapy is a novel strategy in the battle against various cancers. It has been successful in treating hematological tumors, yet it still faces many challenges in the case of solid tumors.
View Article and Find Full Text PDFHow cells orchestrate their cellular functions remains a crucial question to unravel how they organize in different patterns. We present a framework based on artificial intelligence to advance the understanding of how cell functions are coordinated spatially and temporally in biological systems. It consists of a hybrid physics-based model that integrates both mechanical interactions and cell functions with a data-driven model that regulates the cellular decision-making process through a deep learning algorithm trained on image data metrics.
View Article and Find Full Text PDFComput Biol Med
June 2023
To unravel processes that lead to the growth of solid tumours, it is necessary to link knowledge of cancer biology with the physical properties of the tumour and its interaction with the surrounding microenvironment. Our understanding of the underlying mechanisms is however still imprecise. We therefore developed computational physics-based models, which incorporate the interaction of the tumour with its surroundings based on the theory of porous media.
View Article and Find Full Text PDFUnlabelled: The correct function of many organs depends on proper lumen morphogenesis, which requires the orchestration of both biological and mechanical aspects. However, how these factors coordinate is not yet fully understood. Here, we focus on the development of a mechanistic model for computationally simulating lumen morphogenesis.
View Article and Find Full Text PDFCell migration is essential for a variety of biological processes, such as embryogenesis, wound healing, and the immune response. After more than a century of research-mainly on flat surfaces-, there are still many unknowns about cell motility. In particular, regarding how cells migrate within 3D matrices, which more accurately replicate in vivo conditions.
View Article and Find Full Text PDFCell motility is essential for life and development. Unfortunately, cell migration is also linked to several pathological processes, such as cancer metastasis. Cells' ability to migrate relies on many actors.
View Article and Find Full Text PDFOrthognathic surgery is performed to realign the jaws of a patient through several osteotomies. The state-of-the-art bone plates used to maintain the bone fragments in place are made of titanium. The presence of these non-degradable plates can have unwanted side effects on the long term (e.
View Article and Find Full Text PDFMechanical environment has a crucial role in our organism at the different levels, ranging from cells to tissues and our own organs. This regulatory role is especially relevant for bones, given their importance as load-transmitting elements that allow the movement of our body as well as the protection of vital organs from load impacts. Therefore bone, as living tissue, is continuously adapting its properties, shape and repairing itself, being the mechanical loads one of the main regulatory stimuli that modulate this adaptive behavior.
View Article and Find Full Text PDFAdvances in methods for determining the forces exerted by cells while they migrate are essential for attempting to understand important pathological processes, such as cancer or angiogenesis, among others. Precise data from three-dimensional conditions are both difficult to obtain and manipulate. For this purpose, it is critical to develop workflows in which the experiments are closely linked to the subsequent computational postprocessing.
View Article and Find Full Text PDFComput Methods Biomech Biomed Engin
April 2021
Different cell migration modes have been identified in 3D environments, e.g., modes incorporating lamellopodia or blebs.
View Article and Find Full Text PDFDespite the relevant regulatory role that nuclear deformation plays in cell behaviour, a thorough understanding of how fluid flow modulates the deformation of the cell nucleus in non-confined environments is lacking. In this work, we investigated the dynamics of cell deformation under different creeping flows as a general simulation tool for predicting nuclear stresses and strains. Using this solid-fluid modelling interaction framework, we assessed the stress and strain levels that the cell nucleus experiences as a function of different microenvironmental conditions, such as physical constraints, fluid flows, cytosol properties, and nucleus properties and size.
View Article and Find Full Text PDFMost pedobarographic studies of microsurgical foot reconstruction have been retrospective. In the present study, we report the results from a prospective pedobarographic study of a patient after microsurgical reconstruction of her foot with a latissimus dorsi flap and a cutaneous paddle, with a 42-month follow-up period. We describe the foot reconstruction plan and the pedobarographic measurements and analyzed its functional outcome.
View Article and Find Full Text PDFThe healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2) has been identified as one of the most powerful osteoinductive proteins.
View Article and Find Full Text PDFAfter bone trauma, the natural response to restore bone function is the formation of a callus around the fracture. Although several bone healing models have been developed, none have effectively perceived early callus formation and shape as the result of an optimal response to a mechanobiological stimulus. In this paper, we investigate which stimulus regulates early callus formation.
View Article and Find Full Text PDFWound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled.
View Article and Find Full Text PDFMechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a high-frequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process.
View Article and Find Full Text PDFWe compared, via a computational model, the biomechanical performance of reamed versus unreamed intramedullary tibial nails to treat fractures in three different locations: proximal, mid-diaphyseal, and distal. Two finite element models were analyzed for the two nail types and the three kinds of fractures. Several biomechanical variables were determined: interfragmentary strains in the fracture site, von Mises stresses in nails and bolts, and strain distributions in the tibia and fibula.
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