Thursday, 22 October 2020
Speaker: Prof. Daniel Garcia-Gonzalez
Stimuli responsive mechanical systems: from biological cells to magneto-active hydrogels
Critically important biological phenomena in health and disease, such as wound healing, cancer metastasis, and embryonic development, are governed by collective cell migration. This highly complex process depends not only on cellular features, but also on different stimuli from the local cell environment. Cell migration is promoted by the combination of physico-chemical cues, including the mechanical properties of the extracellular matrix (ECM). Stiffness gradients within ECM have recently been demonstrated to result into preferred directions of cell migration. To reproduce such processes, in vitro experiments commonly use soft polymeric materials as ECM for the biological system studied. The main limitation of these materials to simulate biological phenomena relates to their incapability of responding dynamically during the process, i.e., during wound healing (internal stresses, change in stiffness, etc). In this regard, to potentially overcome such a limitation, soft materials have experienced a significant advance during the last years. Among these materials, stimuli-responsive hydrogels offer great opportunities for novel applications within this field. However, the design of these stimuli-responsive (i.e., magneto-responsive) materials is rather complex as they combine nonlinear mechanical behaviour, rate dependencies, magneto-active responses and solvent diffusion processes. Here, we first evaluate the specific mechanisms driving directed collective cell migration. To this end, we develop a continuum formulation and its finite element (FE) implementation to test different hypotheses on the cause of spatial heterogeneities during cell migration on heterogeneous-stiffness substrates. Then, we move to magneto-active hydrogels and propose a general constitutive and FE framework to couple magnetics, diffusion and nonlinear mechanics. This framework is particularized and implemented for 3D problems. Overall, these works provide a flexible computational framework to design further cellular substrates by using magneto-active hydrogels to simulate mechanical-dynamic processes such as wound healing.
Daniel Garcia-Gonzalez is a research fellow at University Carlos III of Madrid (UC3M) within the framework of the Talent Attraction program from Comunidad de Madrid and, recently, an ERC Starting Grant. His research career has mainly been developed in the department of Continuum Mechanics and Structural Analysis of University Carlos III of Madrid and the Solid Mechanics group of University of Oxford. In addition, he has carried out several international stays at different renown institutions, i.e., University of Lorraine at Metz, University of Texas at Austin, Carnegie Mellon University, Louisiana State University, Institute of Fundamental Technological Research (IPPT-PAN) atWarsaw and Institute for Experimental Cardiovascular Medicine (IEKM) at Freiburg. His research focuses on continuum mechanics formulations combining mechanics with other physics, and their applications to problems in different engineering fields. In addition, he has worked in characterisation and constitutive modelling of polymers and polymeric composites; magneto-active polymers; multi-physical modelling of biological soft tissues (works on brain mechanics, electrophysiology and collective cell migration); and computational models to address bioengineering studies. During the last two years, he has created the first multidisciplinary collaboration in UC3M between solid mechanics and bioengineering groups, incorporating an extended collaboration network with both research and industrial institutions. Currently, he is consolidating new research lines in stimuli-responsive polymers as well as mechanistically mediated biological processes (both experimental and modelling aspects).
Notesby Bertrand Leturcq and Cécile Patte.
- Mechanics plays an important role in cells migration, with dependency on various elastic and viscous phenomena shown by experiments, like strain rate, temperature, viscous relaxation or anisotropy.
- Linear and non-linear phenomena occurring in the cell substrate relation generate different cell shape deformations and different cell orientations with different time scales. In particular, cells migrate towards the stiffer regions of the substrate, which is explained by propulsion and polarisation forces. The model developed manages to predict the maximal stress traction measured from experimental data.
- As a consequence, it is possible to design magnetoactive materials and control the cellular mechanical environment remotely so as to use different time scales for different functions. For example: microvalves instantly piloted by a magnetic field, a drug delivery by local diffusion on a medium time scale and, ultimately, cell migration using a magnetoactive substrate.
- For magnetic hydrogels, the equations of diffusion, magnetism and mechanics are formulated with respect to large deformations and are solved here in a finite element framework. The results presented show that the volume response is highly linked to the solvent concentration and that the deformations tend to be homogeneous when diffusion is allowed.
- D. Garcia-Gonzalez, A. Munoz-Barrutia.
Computational insights into the influence of substrate stiffness on collective cell migration.
Extreme Mechanics Letters, 40:100928, 2020.
- R. Sunyer, V. Conte, J. Escribano, A. Elosegui-Artola, A. Labernadie, L. Valon, D. Navajas, J. García-Aznar, J. J. Muñoz, P. Roca-Cusachs, X. Trepat.
Collective cell durotaxis emerges from long-range intercellular force transmission.
Science, 353(6304):1157-1161, 2016.
- D. Garcia-Gonzalez, N.S. Race, N.L. Voets, D.R. Jenkins, S.N. Sotiropoulos, G. Acosta, M. Cruz-Haces, J. Tang, R. Shi, A. Jérusalem.
Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations.
Scientific Reports, 8:10273, 2018.
- R. Zhao, Y. Kim, S. A. Chester, P. Sharma, X. Zhao.
Mechanics of hard-magnetic soft materials.
Journal of the Mechanics and Physics of Solids, 124:244-263, 2019.
- D. Garcia-Gonzalez, C.M. Landis.
Magneto-diffusion-viscohyperelasticity for magneto-active hydrogels: rate dependences across time scales.
Journal of the Mechanics and Physics of Solids, 139:103934, 2020.
- N. Bouklas, C. M. Landis, R. Huang.
A nonlinear, transient finite element method for coupled solvent diffusion and large deformation of hydrogels.
Journal of the Mechanics and Physics of Solids, 79:21-43, 2015.
- H. Banerjee; M. Suhail, H. Ren.
Hydrogel Actuators and Sensors for Biomedical Soft Robots : Brief Overview with Impending Challenges.
Biomimetics, 3(3):15, 2018.