Research

Colloidal gels, glasses, and suspensions form over 95% of biological fluids, most pharmaceutical fluids, and are ubiquitous across personal-care, agricultural, and industrial-coating materials. Despite the pervasiveness of these fluid-suspended, microscopically small particles (colloids), many of their behaviors have defied explanation – such as sudden collapse of colloidal gels, vitrification, and their physical role in biological cell function.

My lab unifies mesoscale physics and chemistry with cellular-level biology through novel theoretical modeling and large-scale computational simulations. We work in four areas:  

• Constructing theories predicting the spatial arrangement of Brownian particles in liquids.
• Mechanistically explaining non-equilibrium phase transitions in colloids.
• Large-scale modeling of confined colloidal suspensions.
• Modeling the physics of living cells.

Our ultimate vision  is to use physico-chemical based modeling of whole-cell function to create a platform for deepening understanding of how cells function, uncovering cellular-based disease mechanisms, and discovering corresponding pathways for novel physics-based therapeutics.

Micro-continuum Theory of Complex Fluids

Theoretical modeling of colloids using microhydrodynamics is routine, but application to dense or heterogeneous suspensions is an immense challenge. Our energy methods are a powerful tool to encode complex boundary conditions yet preserve structural detail. Statistical mechanics theories for modeling colloidal suspensions have been previously restricted to equilibrium conditions and statistically homogeneous or bulk suspensions, limiting predictive power to low concentration or relatively simple fluid flow. But many complex fluid flows involve nano-liter quantities, complicated geometries, high concentration, or confinement. My group has built a combined conservation-of-momentum and energy-methods approach that preserves detailed particle microstructure, resulting in a model capable of simultaneously handling flow, many-body interactions, confinement, coupled transport processes, and heterogeneity.

Phase Mechanics

Colloidal gels are ubiquitous because their multiphase structure – millions of micron-sized particles interconnected by physical bonds and suspended in a liquid – imparts reversible liquid-like and solid-like behavior. Colloidal gels form when phase separation fails, freezing the condensing region into a bonded network of strands via a kinetic process thermodynamic theory cannot predict. The consensus view labeled colloidal gels as static, arrested materials that rupture like solids. However, this resulted in long-standing shortfalls in the ability to predict and engineer their behavior. My group developed a model of gel “Phase Mechanics” that explains these behaviors.

“Phase Mechanics” of colloidal gels. Our group constructed the first large-scale computational model of a reversible colloidal gel, along with a suite of micromechanical algorithms to age and interrogate the gel down to the particle scale. From this we proved that reversible gels, which are placed on equilibrium phase diagrams and identified as being in “arrested phase separation,” instead continue to evolve; that age coarsening pushes toward more complete phase separation but simultaneously deepens arrest; and that gel yield is actually a release from so-called arrest and a leap forward in phase separation. We determined the long-sought mechanistic origin of gel collapse: a reactivation of negative osmotic pressure that releases gels from their apparent arrest and furthers their phase separation.  We showed that yield can occur by rupturing fewer than 0.1% of network bonds, which permits many other bonds to relax, triggering a cascade of relaxation. We synthesized our findings into “Phase Mechanics,” a framework for gel birth, aging, death and re-birth that casts each stage as a kinetic path through the phase diagram. Related publications: Zia, Landrum & Russel,  J. Rheol. 2014; Landrum, Russel & Zia, J. Rheol 2016; Padmanabhan & Zia, Soft Matter 2018; Johnson, Landrum & Zia Soft Matter 2018; Johnson, Moghimi, Petekidis & Zia, J. Rheol. 2019;

Vitrification in colloidal glasses. Despite decades of study, the mechanistic process of colloidal vitrification has remained murky. Prevailing theories and experimental reports suffer two fatal flaws: divergence is prescribed to occur and the cooperative motion claimed as the mechanism of relaxation requires large-scale structure that does not exist. Both issues emerge from the difficulty of quenching deep into the glass. My group overcame this barrier by developing a novel size-jump algorithm. With this we showed that dynamics persist up to maximum packing, disproving the notion of divergence or a thermodynamic glass transition. By examining a broad range of wave numbers and monitoring physical displacement, my group’s work established a new mechanism for glassy relaxation: Correlated motion relaxes the glassy plateau and enables long-time, short-range “dense” self-diffusion that relaxes and ages the glass to the intransient state. Related publications: Wang, Li, Peng, McKenna & Zia, Soft Matter 2020; Peng, Wang, Li, Chen, Zia & McKenna, Phys. Rev. E 2018

Damascus colloids. Building and expanding on our expertise in micromechanical models, we aim to create completely new soft solids by intervening in phase “arrest” using quenching and annealing techniques. In collaboration with the Helgeson Lab (UCSB), we are embarking on a combined experimental and theoretical examination of colloidal microstructure evolution during complex kinetic trajectories through regions of phase instability en route to kinetic arrest. Leveraging these ideas to design colloidal soft matter will enable a dramatic expansion of configurable materials for artificial tissue scaffolds, advanced membranes, and shape memory materials.  

Confined & Hydrodynamically Interacting Colloids

Cellular Stokesian Dynamics. Biological cells are packed with macromolecules that diffuse, react, and self-assemble. Modeling these colloidal-scale physics requires accurately representing confinement, reactions, many-body solvent-mediated interactions, patchy attractions, and Brownian motion. Prior attempts neglected confinement, hydrodynamics, Brownian motion, or all three. Our aim was to explicitly model a spherically confined macromolecular suspension with Brownian motion, hydrodynamic interactions, and chemical reactions for a large number of macromolecules at any concentration. Our Cellular Stokesian dynamics model is the world’s first accurate model of a spherically-confined colloidal suspension Related publications: Aponte-Rivera & Zia, Phys. Rev. Fluids 2016; Aponte-Rivera, Su & Zia, J. Fluid Mech. 2018.

We explicitly represent individual macromolecules and their Brownian motion, hydrodynamics, surface chemistry, and patchy attractions while we track reactions, self-assembly, and ordering, resulting in a model biological cell that recovers cytoplasmic streaming, nuclear migration, gradient diffusion, and ternary complex–ribosome reactions. Our work established that diffusion in cells is anisotropic and that hydrodynamic interactions remain strong for all particle sizes and concentrations, disproving prior assertions that hydrodynamics are screened.  We showed that size polydispersity leads to layered particle structure and increases diffusivity. In this way, biological cells can speed up diffusion of smaller biomolecules by surrounding them with larger ones. 

Modeling the Physics of Life

Colloid physics regulate life-essential processes in biological cells. A grand challenge of systems biology is an understanding of cells so complete that all cellular behavior can be determined from the composition and dynamics of constituent biomolecules. Advances in computation and experiments have enabled progress toward this goal, from atomistic models of proteins to de novo synthesis of entire genomes. Connecting single-molecule to cellular behavior requires bridging processes that operate over nanoseconds and nanometers to those spanning minutes and microns. But the physical details and dynamics of this intermediate realm are largely abstracted away in single-cell assays and whole-cell kinetics models. Colloidal physics, which defines the intermediate physico-chemical dynamics of suspensions like cytoplasm, links molecular-scale phenomena like van der Waals forces to cellular-scale diffusion, self-assembly, and aggregation. We use colloid physics to understand how biomolecules instantiate whole-cell behavior; our approach is to select model biological processes – those essential to cell function, conserved across cell types, and implicated in disease – and then to explicitly represent all associated biomolecules.

To study our hypothesis that colloidal mechanisms beyond Brownian motion regulate mRNA translation outside the ribosome in E. coli, we built a novel bio-colloidal framework with nanometer resolution that explicitly represents the transport dynamics of individual biomolecules as they interact and react over whole-cell-function time scales [Maheshwari et al., Cell, in review], the first colloidally accurate model of mRNA translation. We showed that Brownian motion is essential but insufficient to recover experimentally measured elongation rates; we proposed and tested new colloidal mechanisms that close the gap. This is a general framework for discovering how colloid physics predict biological behavior, which can access systems biology timescales by using a kinetics acceleration scheme that takes advantage of reaction timescales being much longer than those of diffusive mixing. Our findings demonstrate the effectiveness of colloidal biology in representing cell processes and illustrates the effectiveness of theoretical modeling in cell biology.