Unravelling cell migration: defining movement from the cell surface

Cell 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. Cells change their migratory strategy based on their phenotype and the properties of the surrounding microenvironment. Cell migration is, therefore, an extremely complex phenomenon. Researchers have investigated cell motility for more than a century. Recent discoveries have uncovered some of the mysteries associated with the mechanisms involved in cell migration, such as intracellular signaling and cell mechanics. These findings involve different players, including transmembrane receptors, adhesive complexes, cytoskeletal components , the nucleus, and the extracellular matrix. This review aims to give a global overview of our current understanding of cell migration

Herramienta de apoyo para cáncer pediátrico

Se presenta una herramienta de apoyo clínico para cáncer pediátrico. Las imágenes de resonancia magnética son analizadas para obtener la vascularización y la celularidad del tumor. A partir de los sets de imágenes se reconstruye la geometría tridimensional. La evolución del tumor se calcula a través de un modelo mecánico

Computational modelling of the mechanical behaviour of protein-based hydrogels.

Protein-based hydrogels have been extensively studied in the field of biomaterials given their ability to mimic living tissues and their special resemblance to the extracellular matrix. Despite this, the methods used for the control of mechanical properties of hydrogels are very limited, focusing mainly on their elasticity, with an often unrealistic characterization of mechanical properties such as extensibility, stiffness and viscoelasticity. Being able to control these properties is essential for the development of new biomaterials, since it has been demonstrated that mechanical properties affect cell behaviour and biological processes. To better understand the mechanical behaviour of these biopolymers, a computational model is here developed to characterize the mechanical behaviour of two different protein-based hydrogels. Strain-stress tests and stress-relaxation tests are evaluated computationally and compared to the results obtained experimentally in a previous work. To achieve this goal the Finite Element Method is used, combining hyperelastic and viscoelastic models. Different hyperelastic constitutive models (Mooney-Rivlin, Neo-Hookean, first and third order Ogden, and Yeoh) are proposed to estimate the mechanical properties of the protein-based hydrogels by least-square fitting of the in-vitro uniaxial test results. Among these models, the first order Ogden model with a viscoelastic model defined in Prony parameters better reproduces the strain-stress response and the change of stiffness with strain observed in the in-vitro tests.APB was supported by MCIN/AEI/10.13039/501100011033/ and by European Union NextGeneration EU/PRT through the project PLEC2021-007709 (ProCanAid) the Aragon Institute for Engineering Research (I3A). SHR gratefully acknowledges the support of the Government of Aragon (Grant no 2019-23). The work of JMGA was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Advance grant agreement ICoMICS No 101018587) and the Spanish Ministry of Economy and Competitiveness, Spain Grant No PID2021-122409OBC21/AEI/10.13039/501100011033/ FEDER, UE. JAC acknowledges funding from the Ministerio de Ciencia e Innovación (MCIN), Spain through grant BIO2017-83640-P (AEI/FEDER, UE). CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIN, Spain and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence, Spain (grant CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011 033). CHL was the recipient of an FPI predoctoral fellowship, Spain (BES-2015-073191).S

Are the Cells Stronger than we Think?

This work presents a novel methodology to calculate the traction forces exerted by the cell in a three-dimensional (3D) Traction Force Microscopy (TFM) set-up. This methodology starts from the images taken in the TFM essay. In addition, the finite strains hypothesis is assumed in order to capture the cell behaviour.Este trabajo presenta una nueva metodología para calcular las fuerzas de tracción ejercidas por la célula durante un experimento de microscopía de fuerza de tracción. El método presentado parte de las imágenes captadas durante el ensayo experimental. Además, se trabaja bajo la hipótesis de grandes deformaciones para poder modelar de manera más precisa el comportamiento celular

Multiscale modeling of bone tissue Mechanobiology

Mechanical 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. Here we review some key results of bone mechanobiology from computational models, describing the effect that changes associated to the mechanical environment induce in bone response, implant design and scaffold-driven bone regeneration

Confined cell migration and asymmetric hydraulic environments to evaluate the metastatic potential of cancer cells

Metastasis, a hallmark of cancer development, is also the leading reason for most cancer-related deaths. Furthermore, cancer cells are highly adaptable to microenvironments and can migrate along pre-existing channel-like tracks of anatomical structures. However, more representative three-dimensional models are required to reproduce the heterogeneity of metastatic cell migration in vivo to further understand the metastasis mechanism and develop novel therapeutic strategies against it. Here, we designed and fabricated different microfluidic-based devices that recreate confined migration and diverse environments with asymmetric hydraulic resistances. Our results show different migratory potential between metastatic and nonmetastatic cancer cells in confined environments. Moreover, although nonmetastatic cells have not been tested against barotaxis due to their low migration capacity, metastatic cells present an enhanced preference to migrate through the lowest resistance path, being sensitive to barotaxis. This device, approaching the study of metastasis capability based on confined cell migration and barotactic cell decisions, may pave the way for the implementation of such technology to determine and screen the metastatic potential of certain cancer cells

Tumour growth: An approach to calibrate parameters of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment

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. However, the experimental validation of such models represents a challenge to its clinical use as a prognostic tool. This study combines a physics-based model with in vitro experiments based on microfluidic devices used to mimic a three-dimensional tumour microenvironment. By conducting a global sensitivity analysis, we identify the most influential input parameters and infer their posterior distribution based on Bayesian calibration. The resulting probability density is in agreement with the scattering of the experimental data and thus validates the proposed workflow. This study demonstrates the huge challenges associated with determining precise parameters with usually only limited data for such complex processes and models, but also demonstrates in general how to indirectly characterise the mechanical properties of neuroblastoma spheroids that cannot feasibly be measured experimentally

Fluid flow to mimic organ function in 3D in vitro models

Many different strategies can be found in the literature to model organ physiology, tissue functionality, and disease in vitro; however, most of these models lack the physiological fluid dynamics present in vivo. Here, we highlight the importance of fluid flow for tissue homeostasis, specifically in vessels, other lumen structures, and interstitium, to point out the need of perfusion in current 3D in vitro models. Importantly, the advantages and limitations of the different current experimental fluid-flow setups are discussed. Finally, we shed light on current challenges and future focus of fluid flow models applied to the newest bioengineering state-of-the-art platforms, such as organoids and organ-on-a-chip, as the most sophisticated and physiological preclinical platforms