Soft condensed matter comprises a variety of mesoscopic physical systems that are easily deformed by small thermal or mechanical stresses, including liquids, colloids, polymers, liquid crystals, gels, membranes, foams, etc. The relevant length and time scales of these systems are thus naturally larger than those of atoms or molecules, which facilitates experimentally accessing the microscopic states of these systems to understand and predict their emergent macroscopic properties, using the framework of statistical mechanics. Using vibrated granular particles, a variety of fluid patterns with orientational order that resemble equilibrium liquid-crystal phases were found, exhibiting topological defects due to confinement, much as molecular liquid crystals (Figure 20). This system represents a novel approach to study order in 2D fluids of hard particles.
Biological systems are also soft and built on the rich diversity of mesoscale structures mentioned. A tissue is a soft hydrogel, a hierarchical dynamic structure composed by many cells, which in turn are made up of many molecular assemblies orchestrating processes at different length and time scales. These systems set the most outstanding challenge in our goal to understand the spontaneous self-assembly of matter. Bottom-up approaches to recreate biological systems may enable to isolate fundamental physical principles from the complex set of signaling and metabolic pathways of natural systems. With this in mind, we have recently transferred microfluidic technologies from Harvard to IFIMAC, to fabricate vesicles as cell mimetics with exquisite control, enabling to study physical phenomena such as adhesion, fusion, and motility in model systems. These vesicles can also mimic the complex organization of the cell cytoplasm. IFIMAC researchers have used this technology to fabricate vesicles enclosing aqueous compartments to study the effect of permeable membranes in phase separations (Figure 21). Importantly, these vesicles may also find applications in biomedicine, pharmacy, and cosmetics.
Moreover, biological systems are active, they constantly produce and consume energy, which results in the emergence of sometimes unintuitive collective properties. The emergent subdiscipline of Active Matter focuses on understanding such collective properties, which frequently requires out-of-equilibrium physics descriptions. Using bacteria, modeled as run-and-tumble particles, IFIMAC researchers are studying the emergence of collective motion in confined environments (Figure 22).
Molecular Dynamics (MD) simulations are a powerful tool to understand biological processes at the atomic scale. IFIMAC researchers are applying them to the study of proteins, nucleic acids and viruses in their native liquid environment. The elasticity of double-stranded DNA (dsDNA) is a key molecular determinant in the many cellular contexts in which this molecule is found, as it affects the binding affinity of dsDNA with proteins as well as the dsDNA response to the mechanical action exerted by proteins. Using all-atom MD simulations, IFIMAC researchers have proposed that parts of the DNA sequence act as a physical code that controls the structure and mechanical properties of dsDNA at short scales, paving the way for protein-DNA interaction and organization of the genomic material (Figure 23). This work has been extended to dsRNA, where they identified a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that strongly bend the RNA double-helix. This result may be exploited in the emerging field of RNA nanotechnology and might also constitute a natural mechanism for proteins to achieve recognition of specific dsRNA sequences.
IFIMAC has a strong tradition in the construction and use of scanning probe microscopes, in particular in Atomic Force Microscopy (AFM). One of the most exciting applications of AFM is the characterization of biological material at the single-particle level. Physical Virology, the study of viruses usually involve bulk experiments, which gather average data from large ensembles of structures, thus considering all the particles as indistinguishable. However, biochemical processes are highly asynchronous and intermediate states are poorly populated. Therefore, average measurements might conceal details of the processes taking place in viruses. AFM allows the imaging and manipulation of individual virus particles adsorbed on a surface in liquid milieu by using a sharp tip (~10 nm) located at the end of a microcantilever. In this way, IFIMAC researchers study the electrostatic charge of virus structures, monitor differences between wild type and mutant viruses during disassembly, and resemble the disruption process of viruses taking place during infection (Figure 24). Some of these studies are supported by MD simulations using coarse-grained models and simulation codes developed at IFIMAC.
