Research

The Takatori Lab combines theory/computation with bottom-up experiments to understand and engineer soft materials with unusual physical 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.

Engineering a dynamic interface

In nature, contact interfaces between adjacent cells are regulated by specialized membrane-tethered proteins that bind across opposing plasma membranes. To control mass and energy diffusion across these junctions, cells use molecular motors and biopolymers to push against the membrane to modulate the bonding strength between the adhesive membrane surfaces. These nonequilibrium forces enable cell assemblies to achieve exquisite control over bonding capabilities. A technology to achieve a similar level of hierarchical control over the surface bonding in synthetic materials may trigger the development of robust materials with selective fluid and energy transport functionalities. In our research, we aim to advance our basic understanding of self-assembly and emergent phenomena in membrane-based materials that are perturbed away from equilibrium, and use this understanding to achieve exquisite control over molecular bonding and hierarchical structures in synthetic materials.

To achieve a theory-driven synthesis of colloidal assemblies, our approach will combine analytical theory, MD simulations, and bottom-up reconstitution experiments. The richness of our theory may be appreciated by considering the coupling between colloidal dynamics, nonequilibrium active forces, and surface biopolymer evolution. A key feature of our problem is the multiscale, hierarchical coupling between macroscale colloidal dynamics and molecular interfacial dynamics.

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Illustration by David S. Goodsell, the Scripps Research Institute

Molecular dynamics simulations to elucidate polymer brush dynamics.

 

​​This project is inspired by our previous biophysical work on the plasma membrane of mammalian cells, which 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 plasma membrane.  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).  We use many of these concepts in the project above to create synthetic materials.

 

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). The kinetics and thermodynamics of macromolecular interactions at the cell surface interface play a critical role in these physiological processes.

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Interaction between an immune cell and a target cell is an example of a "dynamic interface".

 

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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.  In this project, we study the transport dynamics of self-propelled active species within heterogeneous, porous, complex media. Our inspiration is the dynamics of living bacteria within mucus hydrogels or biofilms, which consist of highly entangled, crosslinked polysaccharise polymers, protein crosslinkers, lipids, and extracellular DNA.  Through nature’s trial-and-error, living bacteria have optimized when, where, and how to tune their behavior within complex environments.

 

We combine hydrodynamic theories, statistical mechanics, and optical microscopy to develop a microscopic and mesoscale understanding of multiphase active particulate transport within complex materials.

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Dynamics of living particles in complex material environments

Experiments

Simulations

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How do living bacteria physically and chemically interact with polymers?

 

Molecular-level dynamics

Theory

Transport dynamics + Macroscopic material properties

Brief overview of research area:

 

Evolution of glassy-like colloidal 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. 

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Passive materials

Activity

Activity-derived materials

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Takatori SC*, De Dier R*, et al., Nat Commun, 2016.

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Previous work: Swim Pressure of Active Matter

Developed a mechanical theory to understand stress generation in active matter suspensions.  The 'swim pressure' has become a nice framework to understand many nonequilibrium phenomena in active systems.

Seminar at Caltech to the general scientific audience. 

Our current work has taken quite a random walk from this initial work: