Physics and Chemistry of Living Systems
Takatori Lab combines theory/computation with bottom-up experiments to understand and engineer nature-inspired soft materials with superior mechanical qualities.
Many energy, environment, and human health applications demand precise control over length and time scales of physical and chemical processes. While many processes operate at thermodynamic equilibrium and are driven by forces that are thermal in nature (i.e., 'kT'), many biological systems have evolved the use of non-conservative active forces to finely control how quickly, how often, and with what magnitude a physical or chemical process should occur. In particular, nature's use of nonequilibrium forces such as division, motility, and adaptive response enable living systems to produce advanced soft materials. As chemical engineers, we strive to harness these design rules to enable fine control over the transport phenomena, thermodynamics, and kinetics in processes relevant to human health and industry.
A gold standard of chemical and materials engineering is to understand how molecular arrangement and transport influence macroscopic, measurable quantities like strength, viscosity, toughness, and brittleness. That way, we know exactly how one should tune the molecular structure to achieve desired engineering performance. One class of material that we explore from this materials perspective are microbial communities and bacterial biofilms, which are collections of cells that are held together by highly entangled, crosslinked polysaccharise polymers, protein crosslinkers, lipids, and extracellular DNA. Through nature’s trial-and-error, the bacteria have optimized when, where, and how to form these communities so that they are resilient to environmental stresses.
We use optical microscopy, force microscopy, microrheology, microfabrication, and microfluidics to measure mechanical properties of bacterial communities. We invoke statistical mechanics to develop microscopic theories that elucidate how cells control and modulate the strength and viscosity of their surrounding environment.
Our goals are to (1) understand how bacteria create tough, adaptive materials, (2) engineer strategies to remove or protect bacterial communities, and (3) apply these principles to engineer new synthetic materials.
Materials science of microbial communities and bacterial biofilms
Bellin et al., Nat Commun, 2014
How do living bacteria physically and chemically interact with polymers?
Macroscopic material properties: strength, viscosity, ductility, etc.
Very brief overview of research area:
Dynamics of protein and polysaccharide polymers on cell surfaces
The plasma membrane of mammalian cells is often (erroneously) depicted as a flat, empty (boring?) sheet of phospholipid bilayer embedded with a few stumps of transmembrane proteins. These representations do not do justice to the wonderful diversity and rich complexities of the cell surface. In reality, most cells have a densely packed array of surface proteins (~10 - 20000 / square micron) and polysaccharides that extend far beyond the surface of the lipid bilayer, as depicted below. This external coating, called "glycocalyx", is essential for cell-cell recognition and intercellular communication. Furthermore, the membrane is highly dynamic -- the lipid bilayer fluctuates from thermal noise of the solvent and active forces generated by cellular processes (like actin polymerization). The focus of this research area is to determine how the glycocalyx and membrane dynamics physically impact key physiological processes.
Illustration by David S. Goodsell, the Scripps Research Institute
We conduct molecular dynamics simulations to elucidate polymer brush dynamics.
Takamori et al. Cell 2006.
We conduct bottom-up and top-down biomolecular experiments to identify the role of glycocalyx on physiological function.
The glycocalyx may be interpreted as a classical polymer brush, except that the individual polymers are bound to an in-plane fluid membrane that allows the polymers to diffuse in 2D along the surface (and fluctuate in the transverse direction). In-plane fluidity results in many interesting phenomena that are absent in traditional grafted polymer brushes. For example, for an immobile surface, the only way a colloidal solute in the bulk can reach the surface is by compressing the brush. For an in-plane fluid membrane, the brush may instead diffuse away from the interface and pay the small penalty of crowding the exterior surface and avoid the large entropic loss of compression.
In fact, there are many physiological processes where macromolecules need to achieve physical contact with the membrane; examples include the engagement of short receptors and ligands on apposing cell surfaces (e.g., macrophage with a foreign body), red blood cell coagulation, and influenza virus entry and fusion with host cells (which we want to prevent). We wish to understand the mechanical properties of the cell surface and identify how polymer dynamics of the glycocalyx impact key physiological processes.
(1) We use MD simulations to compute thermodynamic and kinetic barriers in the free energy landscape. (2) We engineer bottom-up, in-vitro experiments with purified biomolecules to elucidate physical concepts. (3) We conduct top-down experiments on mammalian cells to demonstrate physiological function of underlying physical phenomena.
This problem may be understood in the framework of classical chemical reaction engineering and heterogeneous catalysis. The rate-limiting-step of adsorption of a solute to the membrane surface may be dominated by slow reaction, mass transfer limitation, or both. There is a kinetic competition between mass transfer through the brush and the mobility of proteins and glycocalyx on the membrane (which is affected by coupling to the underlying cytoskeleton). What methods do cells use to control this transport and kinetics? Is there a 'catalyst' for this process?
Buckling and deformation of fluid membranes at cell interfaces
The cytoskeleton is a network of protein polymers that provides the cell with mechanical support and regulates many biochemical processes at membrane interfaces. In-vitro experiments conducted in the lab have shown that mechanical coupling between fluid membranes and reconstituted actomyosin generate buckling instabilities on the membrane. These findings demonstrate the potential importance of mechanical forces in cellular signaling and shaping the complex structure of membrane-bound organelles like the ER, Golgi apparatus, and mitochondria. The coupling of mechanical forces generated by actin polymerization and the dynamics of cell membranes is relevant in the project discussed above.
Phospholipid membranes deform and produce membrane tubes when interacting with reconstituted actin filaments.
Colloidal hydrogels and dense amorphous suspensions
Use of nonconservative active forces for materials design
In soft materials, many important thermodynamic transitions are dominated and limited by kinetics; for example, crystallization, vitrification, smectic/nematic ordering, etc. Some thermodynamic phases can be impractical to explore because the microstructure is kinetically arrested and/or structural rearrangement is too slow when relying upon thermal Brownian forces alone. By injecting the material with a source of non-thermal active agitation, we aim to accelerate the formation of new materials and expand the range of what is possible to engineer.
Takatori SC*, De Dier R*, et al., Nat Commun, 2016.
Seminar at Caltech to the general scientific audience.
Our current work has taken quite a random walk from this initial PhD work: