Abstract
Recent research on biological materials and bioartificial systems has created one of the most dynamic field at the confluence of physical sciences, molecular engineering, cell biology, materials sciences, biotechnology and (nano) medicine. This field concerns better understanding of living systems, design of bio-inspired materials, synthesis of bioartificial technologies with new properties depending on their multi-scale architectures. Biological and man-made systems show the first level of organization at the nanoscale, where the fundamental properties and functions are settled (e.g., proteome and genome). The nanoscale properties reflect on larger scales: mesoscale, microscale, and continuum. Mechanisms by which phenomena at the different length and time scales are coupled and influence each other is the central issue in linking properties to functionalities, with a dramatic impact in designing and engineering biosystems. To get insights into the progressive trough-scales cascade effects-from molecular to macroscale level and from nanoseconds to life expectancy duration-multiscale/multiphysics models are required, dealing with inorganic, biological and hybrid matter. Thus, bioartificial systems technology depends upon our ability in assembling molecules into objects, hierarchically along several length scales, and in disassembling objects into molecules, in a tailored manner. As a peculiar feature, in bioartificial systems, the definition of the interactions between artificial and biological components needs to incorporate the “time” variable, in order to reproduce the evolution of the overall system, and to simulate complex phenomena as biodegradation and tissue remodeling. Herein, a number of paradigmatic multiscale models that attend the investigation of biological systems and the engineering of bioartificial systems is reviewed and discussed.
Publisher
Trans Tech Publications, Ltd.
Subject
Mechanical Engineering,Mechanics of Materials,Condensed Matter Physics,General Materials Science
Reference35 articles.
1. The authors evaluated the elastic constants of each tubulin monomer, together with the interaction force between them by means of molecular dynamics (MD) simulations. Using the MD results, they modeled a 1 μm long MT as a cylinder constituted by interacting elastic elements and examined its properties via finite element method (FEM). In other studies, Deriu and co-workers [5-6] investigated the mechanics of actin filaments and microtubules, by combining MD simulations with Elastic Network Modeling (ENM) and Rotation Translation Block (RTB) normal mode analysis. This modeling strategy allowed to reproduce the mechanics of F-actins and MTs, in terms of bending, stretching and torsional stiffness, with a very high level of accuracy, taking into account the contribute of the entire number of residues and using full atomistic models, with no need to introduce empirical parameters. The mechanics of F-actin and MTs was expressed as a result of localized molecular rearrangements, driven by thermal fluctuations, providing an elucidation of the characteristics of their flexibility on the basis of the intermonomer interactions in the assemblies. Interestingly, MTs have shown to grow stiffer as they grow longer, a peculiar property of these structures that could lead to advances in nano-materials development. Crosslinked actin networks were studied by Kim and co-workers.
2. using BD simulations combined with coarse-graining procedures, in which cylindrical segment represented several monomers of F-actin. Surprisingly, the authors found that thermal fluctuation plays little role in viscoelasticity of these systems, so that the network consisting of crosslinked F-actins can be viewed essentially as a deterministic overdamped system in a viscous medium. A multiscale procedure was also employed by Qin and co-workers.
3. for the investigation of vimentin IFs. Atomistic level MD were combined with coarse grained simulation, allowing to identify links between IF structure and deformation mechanisms at distinct hierarchical levels. The multi-scale structure of IFs resulted crucial for their characteristic mechanical properties, in particular their ability to undergo severe deformation of ≈300% strain without breaking, facilitated by a cascaded activation of distinct deformation mechanisms operating at different levels. Summarizing, results from the application of multiscale modeling approaches on cytoskeleton filaments have enabled a new paradigm in studying the mechanical properties of these structures. An important implication of the deformation studies of the cytoskeleton filaments reviewed here is the elucidation of fundamental mechanisms of mechanical deformation, which helps us to better understand the physiological stress response of these biological systems. Cytoskeleton filaments may be considered as model systems to fabricate novel engineered materials that display a high sensitivity to applied forces, show flaw tolerant properties, provide a rapid route to self-assembly, and combine biological compatibility with the possibility to achieve multifunctional and mutable material properties.
4. Such materials could be used as biomaterials for clinical applications, or as novel efficient energy-absorbing materials. There are recent reports in which the hierarchical paradigms of other biological systems, i. e. amyloid proteins, has been applied in the development of a novel biomaterial. Knowles and co-workers.
5. recently reported a novel approach to make multifunctional hierarchical biomaterials by exploiting the self-assembling properties of amyloid fibrils. The amyloid protein fibrils were cast into thin films, aligned and stacked in the plane of the film to form a strong material (with both nano- and micro-meter scale order) that could interact with visible light. The functional properties of this biomaterial stem from the capacity to tune optical properties by changing the alignment of amyloid fibrils at the mesoscale. For future research, of particular interest could be the implementation of the ability to switch the structure of the material at different levels of the hierarchy using external signals such as temperature, pH, magnetic or electric fields. This research could be supported by in silico techniques based on multiscale modeling tools, in order to describe the mechanisms of these complex structures at the different scales of organization, both in space and time. Some applications of mechano-mutable biomaterials are: small-scale valves (from the nanoscale upwards), sensors and actuators, or even platforms for spatially and temporally controlling the growth of cells. Multiscale modeling of artificial and bioartificial materials and systems Multiscale modeling approaches are emerging as important techniques to study artificial and bioartificial materials and systems. A detailed knowledge about the physics and chemistry of artificial and bioartificial materials and systems, at different length and time scales, is essential to tailor their macroscopic physical and mechanical properties. A better understanding of these issues could be helpful also to optimize their processing and, thus, their elucidation can be decisive for their final industrial application. Multiscale modeling approaches have been recently employed to study the influence of the local structural properties at the interphases of multiphase materials on their overall mechanical response. Moreover, multiscale modeling strategies have been employed to investigate the behavior of complex microelectromechanical systems (MEMS) and bioreactors, where the coupling of different physical processes in space and time represent the basis of their operating mechanisms. Here we report some examples of multiscale modeling approaches to polymeric systems, artificial biomoleculars detectors and bioreactors. Baeurle and co-workers have develop a new multiscale modeling method, which combines the self-consistent field theory approach with the kinetic Monte Carlo method, to simulate the structural and dynamical evolution taking place in thermoplastic elastomers, where hard glassy and soft rubbery phases alternate. Koelman and co-workers.