Session R12: Macromolecular Phase Separation IV

Live

We investigated how nanoparticle additives with extremely different inter-particle interactions affected the phase transition of strongly confined semiflexible polymer (SFC) solutions. We used GPU-accelerated Langevin dynamics simulation to explore how adding purely repulsive hard nanoparticles (HNP) and non-interacting ideal nanoparticles (INP) affected inter-polymer alignment and the isotropic-nematic transition. Polymers are modeled as semi-flexible chains with beads of diameter s_m=1, persistence length P=20 and contour length L=25. The NPs are spheres with s_p =2.5. The mixture is confined in a thin slit of height H=4.
We observed that adding low volume fraction $\phi_p$ of HNP dispersed the polymer matrix. disrupted inter-polymer alignement, and upshifted the critical volume fraction $\phi_cr$. In contrast, INP induced depletion attraction between polymers, enhanced polymer alignment, and always facilitated the I-N transition. For moderate or high $\phi_p$, hard NPs would crystalize and phase separate from the nematic polymer micro-domain. On the other hand, ideal NPs formed a liquid micro-domain that decreased in size as the monomer volume fraction $\phi_m$ increased.   

Live

The organization of multiple subcellular compartments is controlled by biopolymer-related liquid–liquid phase separation. Aqueous two-phase systems formed by two non-ionic polymers may serve as a simple model for phase separation in cells. Phase separation occurs with the emergence of interfacial tension. To better understand liquid–liquid phase separation mechanisms, interfacial tension was measured in aqueous two-phase systems with different additives. Interfacial tension depends on differences between the solvent properties of the coexisting phases, which were measured to quantify dipole–dipole, ion–dipole, ion–ion, and hydrogen bonding interactions. Additional measurements using FTIR showed that solvent properties are dependent on the structure of water. Based on our current measurements and literature data, we propose a mechanism for phase separation in aqueous two-phase systems.   

Live

Multiphase liquid droplets in the cell allow for spatial compartmentalization of biomolecules which support different chemical processes in each region. Inspired by the core-shell structures of various membrane-less organelles, we seek to better understand the thermodynamic limits to the number of phases which can simultaneously exist outside the confines of a cell, and the complex morphological structures they can create. Using a model DNA liquid system, we construct multiple immiscible liquids by exploiting the sequence-specific nature of DNA hybridization. We discuss how tuning surface tension can allow different mesoscale droplet structures to be realized.   

Live

The knowledge of solubility has a significant role in many areas of research including pharmaceutical industry. The solubility can be estimated from the calculation of free energy of solvation. Also, the interaction between molecules can be understand from diffusion phenomenon. In this work, we have performed classical molecular dynamics simulations of amoxicillin in two solvents: water and ethanol. The free energy of solvation of amoxicillin in water and ethanol have been estimated at 310 K temperature from thermodynamic integration (TI) and Bennett’s acceptance ratio (BAR) methods. The self diffusion coefficients of both amoxicillin and water have been estimated using Einstein’s relation; and their binary diffusion coefficient using Darken's relation at different temperature. In addition, the effect of system size on diffusion coefficient has been studied; and the viscosity coefficient of water and solution of amoxicillin in water have been estimated at 298 K temperature.   

Live

We propose a continuum theory of the liquid-liquid phase separation in an elastic network where phase-separated microscopic droplets rich in one fluid component can form as an interplay of fluids mixing, droplet nucleation, network deformation, thermodynamic fluctuation, etc. We find that the size of the phase-separated droplets decreases with the shear modulus of the elastic network with a scaling factor of -1/3 and the number density of the droplet increases almost linearly with the shear modulus, which are verified by the experimental observations. Phase diagrams in the space of (fluid constitution, mixture interaction, network modulus) are provided, which can help to understand similar phase separations in biological cells and also to guide fabrications of synthetic cells with desired phase properties.   

Live

Single molecule tracking has been employed to investigate the statistics of molecular components entering and leaving membraneless compartments. These compartments often form in cells by phase separation of proteins and provide centers for a variety of biochemical processes. Interpreting such single molecule data requires a theory that links molecular trajectories to the properties of phase separation at larger scales.
Starting from a continuum theory of macroscopic phase separation we derive a Langevin equation for molecular trajectories that takes into account thermal fluctuations.
We find that a molecule experiences an effective potential, which has a steep gradient at phase boundaries. We obtain the position-dependent diffusion coefficient and the drift velocity, which is caused by concentration fluxes.
We discuss how the physics of phase separation affects the statistics of molecular trajectories. We show that our approach can be used to infer key phase separation parameters from the statistics of single-molecule trajectories.
Finally, we show that, when the system is not at equilibrium, detailed balance is broken at the level of molecular trajectories. Such trajectories can thus be used to characterize non-equilibrium features of intracellular condensates.   

Live

The kinetics of nucleation and growth of liquid droplets are recently acquired some biological significance since its implications of the phase separation of protein with living cells. However, this process in the presence of an elastic filament network remains poorly understood. We investigated such a phase separation process by a Brownian dynamics simulation of a size-changeable disk, where the disk size depends on the mechanical forces from the network and chemical potential of the minority phase. The translational movement of the disk is governed by its interaction with cross-linked Gaussian potential. The results give us insight into how droplet growth against the retardation of the filament in different regimes and how the network enhances the diffusion of the disk.   

Live

Collagen fibrils are nanoscale biological ropes with a diameter between 50 and 500 nm. They are the main constituent of load bearing tissues and are known to be strong under tension. Fibrils can also be very long in some tissues, up to millimeters in length, which means that they are in principle prone to buckling and torsional instabilities. One way to study buckling of a rigid rod is to attach it to a stretched elastic substrate that is then returned it to its original length. We extract single collagen fibrils from bovine tendons and absorb them on a pre-stretched silicon rubber. We characterize the shape of the fibrils after and during strain release using atomic force microscopy, optical microscopy and second harmonic generation microscopy. We observe both the well-characterized short wavelength sinewave buckling mode and two types of torsional instabilities, writhing and bird-caging. The onset of buckling and bird-caging occurs at substrate pre-stretch around 1 to 3%. This high susceptibility to compression has implications on the way collagen fibrils are organized within tissues.   

Live

Protein-rich condensates in living cells can wet the cell membrane and surfaces of membrane-bound organelles. In cells, proteins are also known to bind to membranes leading to a molecular layer of bound molecules. It is not clear how binding affects the physics of surface phase transitions such as wetting and prewetting. Here, we derive the corresponding continuum theory for a three-dimensional bulk in the presence of a two-dimensional membrane. We find that membrane binding gives rise to multiple prewetting transitions and a shifted wetting transition line. Strikingly, the coupling between membrane and bulk can shift the prewetting line far away from binodal which facilitates prewetting already at very low bulk concentrations. Our work suggests that the physics of surface phase transitions combined with molecular binding can play an important role to control the formation of protein-rich phases at intra-cellular surfaces.   

Live

Here we present reciprocal-space self-consistent field (SCF) calculations of the Frank-Kasper (FK) phases formed by diblock copolymer (DBC) melts based on the model used in dissipative particle dynamics (DPD) simulations, following the method of Matsen (Macromolecules 45, 8502 (2012)). Comparisons with the SCF results based on the “standard” model (i.e., incompressible melts of continuous Gaussian chains with the Dirac d-function interaction) clearly reveal the effects of model differences (i.e., discrete Gaussian chains, finite-range interactions, and compressibility) on the stability of FK phases. This also enables us to unambiguously quantify using DPD simulations the fluctuation/correlation effects inherently neglected by the SCF theory, which are important to the low-molecular weight DBCs forming such phases in experiments.   

Live

Canonical statistical analysis has long been employed successfully in studies of systems that satisfy the criteria for the thermodynamic limit. However, this approach may lead to false signals for finite systems that cannot be scaled up, but still show clear transition features. The recently introduced generalized microcanonical inflection-point analysis method [1] allows for the systematic identification and classification of transitions in systems of any size. We use this method to extend previous simulation studies of a coarse-grained model for flexible polymers [2] and analyze structural transitions in semiflexible polymers. For this purpose, we performed extensive parallel replica-exchange Monte Carlo simulations and measured the density of states needed for the microcanonical analysis with high accuracy.

[1] K. Qi and M. Bachmann, Phys. Rev. Lett. 120, 180601 (2018).
[2] K. Qi, B. Liewehr, T. Koci, B. Pattanasiri, M. J. Williams, and M. Bachmann, J. Chem. Phys. 150,
054904 (2019).   

On Demand

A new lattice model is designed to be suitable for simulating low-molecular-weight block copolymer (BCP) melts currently used in experiments to achieve sub-10nm domain sizes (i.e., having an invariant degree of polymerization between 10² and 10³). It gives an isothermal compressibility comparable to real polymers such as poly(styrene) and poly(methyl methacrylate), high Monte Carlo simulation efficiency, and the fluctuation effects important for the low-molecular-weight BCPs. With its high lattice coordination number, the model can also be readily used for branched chains such as star BCPs. When the Shaffer’s method of preventing bond-crossing (J. Chem. Phys. 1994, 101, 4205) is implemented, it can further be used to study simultaneously the static and dynamic properties of low-molecular-weight BCPs needed for nanolithography.