Insigneo Seminar: modelling arterial chemo-mechanobiology
Thursday, 2 May, 11:00 am - 12:00 pm BST
We are delighted that Dr Michele Marino, Group Leader “Predictive Simulations in Biomechanics” at the Institute of Continuum Mechanics, Leibniz Universität, will be attending the Insigneo Insitute to give a seminar on ‘modelling arterial chemo-mechanobiology’ on Thursday 2 May 2019 (time and location to be confirmed).
Chemo-mechano-biological modelling of damage and growth-and-remodelling in arterial tissues
by Michele Marino
Under homoeostatic conditions, the deposition and degradation of constituents of soft tissues balance each other. From a mechanobiological perspective, this is the result of the balance between molecular signaling pathways driven by cell-cell interactions. In mechanobiological theories, one of the goals of living cells when subjected to physiological loading conditions is the maintenance of a homoeostatic state of stress. On the other hand, loading conditions above the physiological limit cause injury. Injury activates a cascade of cell-cell interactions whereof the goal is to replace damaged constituents. Inflammatory mechanisms are triggered and determine a cascade of events leading to the production and resorption of a number of enzymes (e.g., MMPs) and/or growth factors (TGF-). In other words, a speed up of growth and remodelling (G&R) mechanisms occur as a consequence of injury. Moreover, since many molecular species are in common, inflammatory responses might affect also the chemo-biological pathways of the physiological G&R. In other words, injury is a source of imbalance for the delicate equilibrium which determines the arrangement and content of tissue constituents at hand. This might lead to a compromise of the macroscopic functionalities of biological structures, and hence to the onset and the progression of pathologies. For instance, this is the case of in-stent restenosis (ISR), that is the re-narrowing of the vessel induced by a pathological tissue growth following the implantation of stents in the treatment of arterial atherosclerosis.
This lecture shades a light on the coupling between injury and G&R under specific pathological conditions. A chemo-mechano-biological theoretical model and its computational implementation is proposed. Arterial deformation gradient is decomposed into an elastic and a plastic part in order to account for tissue damage; transport problems modelling cell-cell signaling pathways are introduced; G&R laws are defined in order to account for the rearrangement of tissue constituents as a consequence of active molecular pathways. Numerical simulations are presented for verifying the developed computational tool, for validating the proposed damage model by means of a novel experimental technique based on collagen hybridizing peptides, as well as for highlighting the role of injury on the pathological activation of G&R in diseases.