Publications
89 results found
Pytowski L, Lee CF, Foley AC, et al., 2020, Liquid–liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation, Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424
Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic–hydrophilic interfaces (e.g., air–water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic–hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid–liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.
Lee CF, 2020, Formation of liquid-like cellular organelles depends on their composition, NATURE, Vol: 581, Pages: 144-145, ISSN: 0028-0836
Partridge B, Lee CF, 2019, Critical motility-induced phase separation belongs to the Ising universality class, Physical Review Letters, Vol: 123, ISSN: 0031-9007
A collection of self-propelled particles with volume exclusion interactions can exhibit the phenomenology of gas-liquid phase separation, known as motility-induced phase separation (MIPS).The non-equilibrium nature of the system is fundamental to the phase transition, however, it is unclear whether MIPS at criticality contributes a novel universality class to non-equilibrium physics.We demonstrate here that this is not the case by showing that a generic critical MIPS belongs tothe Ising universality class with conservative dynamics.
Sartori P, Lee CF, 2019, Scaling behaviour of non-equilibrium planar N-atic spin systems under weak fluctuations, NEW JOURNAL OF PHYSICS, Vol: 21, ISSN: 1367-2630
Sartori P, Lee CF, Scaling behaviour of non-equilibrium planar N-atic spin systems under weakuctuations, New Journal of Physics, ISSN: 1367-2630
Starting from symmetry considerations, we derive the generic hydrodynamic equation of nonequilibrium XY spin systems with N-atic symmetry under weak fluctuations. Through a systematictreatment we demonstrate that, in two dimensions, these systems exhibit two types of scalingbehaviours. For N = 1, they have long-range order and are described by the flocking phase of drypolar active fluids. For all other values of N, the systems exhibit quasi long-range order, as in theequilibrium XY model at low temperature.
Overby DR, Spenlehauer A, Cairoli A, et al., 2019, Actomyosin contractility and the vimentin cytoskeleton influence giant vacuole life-cycle in Schlemm's canal endothelial cells, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Weber C, Zwicker D, Juelicher F, et al., 2019, Physics of active emulsions, Reports on Progress in Physics, Vol: 82, Pages: 1-40, ISSN: 0034-4885
Phase separating systems that are maintained away from thermodynamic equilibrium via molecular processes represent a class of active systems, which we call \textit{ active emulsions}. These systems are driven by external energy input for example provided by an external fuel reservoir. The external energy input gives rise to novel phenomena that are not present in passive systems. For instance, concentration gradients can spatially organise emulsions and cause novel droplet size distributions. Another example are active droplets that are subject to chemical reactions such that their nucleation and size can be controlled and they can spontaneously divide. In this review we discuss the physics of phase separation and emulsions and show how the concepts that governs such phenomena can be extended to capture the physics of active emulsions. This physics is relevant to the spatial organisation of the biochemistry in living cells, for the development novel applications in chemical engineering and models for the origin of life.
Chen L, Lee CF, Toner J, 2018, Incompressible polar active fluids in the moving phase in dimensions d>2, New Journal of Physics, Vol: 20, ISSN: 1367-2630
We study universal behavior in the moving (polar ordered) phase of a generic system of motile particles with alignment interactions in the incompressible limit for spatial dimensions d > 2. Using a dynamical renormalization group analysis, we obtain the exact dynamic, roughness, and anisotropy exponents that describe the scaling behavior of such incompressible systems. This is the first time a compelling argument has been given for the exact values of the anomalous scaling exponents of a flock moving through an isotropic medium in d > 2.
Lee C, Wurtz JD, 2018, Novel physics arising from phase transitions in biology, Journal of Physics D: Applied Physics, Vol: 52, ISSN: 0022-3727
Phase transitions, such as the freezing of water and the magnetisation of a ferromagnet upon lowering the ambient temperature, are familiar physical phenomena. Interestingly, such a collective change of behaviour at a phase transition is also of importance to living systems. From cytoplasmic organisation inside a cell to the collective migration of cell tissue during organismal development and wound healing, phase transitions have emerged as key mechanisms underlying many crucial biological processes. However, a living system is fundamentally different from a thermal system, with driven chemical reactions (e.g. metabolism) and motility being two hallmarks of its non-equilibrium nature. In this review, we will discuss how driven chemical reactions can arrest universal coarsening kinetics expected from thermal phase separation, and how motility leads to the emergence of a novel universality class when the rotational symmetry is spontaneously broken in an incompressible fluid.
Leiming C, Lee CF, John T, 2018, Squeezed in three dimensions, moving in two: hydrodynamic theory of three-dimensional incompressible easy-plane polar active fluids, Physical Review E, Vol: 98, ISSN: 1539-3755
We study the hydrodynamic behavior of three-dimensional (3D) incompressible collections of self-propelled entities in contact with a momentum sink in a state with nonzero average velocity, hereafter called 3D easy-plane incompressible polar active fluids. We show that the hydrodynamic model for this system belongs to the same universality class as that of an equilibrium system, namely, a special 3D anisotropic magnet. The latter can be further mapped onto yet another equilibrium system, a DNA-lipid mixture in the sliding columnar phase. Through these connections we find a divergent renormalization of the damping coefficients in 3D easy-plane incompressible polar active fluids, and obtain their equal-time velocity correlation functions.
Lee C, Lee C, 2018, Equilibrium kinetics of self-assembling, semi-flexible polymers, Journal of Physics: Condensed Matter, Vol: 30, ISSN: 0953-8984
Self-assembling, semi-flexible polymers are ubiquitous in biology and technology. However, conflicting accounts of the equilibrium kinetics remain for such an important system. Here, by focusing on a dynamical description of a minimal model in an overdamped environment, I identify the correct kinetic scheme that describes the system at equilibrium in the limits of high bonding energy and dilute concentration.
Lee C, Leanne M, Liu L-N, et al., 2018, Insights into the origin of distinct medin fibril morphologies induced by incubation conditions and seeding., International Journal of Molecular Sciences, Vol: 19, ISSN: 1661-6596
Incubation conditions are an important factor to consider when studying protein aggregation in vitro. Here, we employed biophysical methods and atomic force microscopy to show that agitation dramatically alters the morphology of medin, an amyloid protein deposited in the aorta. Agitation reduces the lag time for fibrillation by ~18-fold, suggesting that the rate of fibril formation plays a key role in directing the protein packing arrangement within fibrils. Utilising preformed sonicated fibrils as seeds, we probed the role of seeding on medin fibrillation and revealed three distinct fibril morphologies, with biophysical modelling explaining the salient features of experimental observations. We showed that nucleation pathways to distinct fibril morphologies may be switched on and off depending on the properties of the seeding fibrils and growth conditions. These findings may impact on the development of amyloid-based biomaterials and enhance understanding of seeding as a pathological mechanism.
Wurtz J, Lee C, 2018, Stress granule formation via ATP depletion-triggered phase separation, New Journal of Physics, Vol: 20, ISSN: 1367-2630
Stress granules (SG) are droplets of proteins and RNA that formin the cell cytoplasm during stress conditions. We consider minimal models ofstress granule formation based on the mechanism of phase separation regulatedby ATP-driven chemical reactions. Motivated by experimental observations, weidentify a minimal model of SG formation triggered by ATP depletion. Ouranalysis indicates that ATP is continuously hydrolysed to deter SG formationunder normal conditions, and we provide specific predictions that can be testedexperimentally.
Wurtz JD, Lee CF, 2018, Chemical-Reaction-Controlled Phase Separated Drops: Formation, Size Selection, and Coarsening, PHYSICAL REVIEW LETTERS, Vol: 120, ISSN: 0031-9007
Lee C, Wurtz JD, Chemical reaction-controlled phase separated drops: Formation, size selection, and coarsening, Physical Review Letters, ISSN: 0031-9007
Nesbitt D, Pruessner G, Lee C, 2017, Edge instability in incompressible planar active fluids, Physical Review E, Vol: 96, ISSN: 1539-3755
Interfacial instability is highly relevant to many important biological processes. A key example arises in wound healing experiments, which observe that an epithelial layer with an initially straight edge does not heal uniformly. We consider the phenomenon in the context of active fluids. Improving upon the approximation used by Zimmermann, Basan, and Levine [Eur. Phys. J.: Spec. Top. 223, 1259 (2014)], we perform a linear stability analysis on a two-dimensional incompressible hydrodynamic model of an active fluid with an open interface. We categorize the stability of the model and find that for experimentally relevant parameters, fingering instability is always absent in this minimal model. Our results point to the crucial role of density variation in the fingering instability in tissue regeneration.
Hong L, Lee CF, Huang YJ, 2017, Statistical Mechanics and Kinetics of Amyloid Fibrillation, Pages: 113-186, ISSN: 1793-1363
Chen L, Toner J, Lee CF, 2017, Universality in Incompressible Active Fluids, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S281-S281, ISSN: 0175-7571
Wurtz JD, Lee CF, 2017, Chemically-driven kinetics of phase separated membrane-free organelles, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S200-S200, ISSN: 0175-7571
Wurtz JD, Lee CF, 2017, Chemically-driven kinetics of phase separated membrane-free organelles, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S63-S63, ISSN: 0175-7571
Weber CA, Lee CF, Juelicher F, 2017, Droplet ripening in concentration gradients, New Journal of Physics, Vol: 19, ISSN: 1367-2630
Living cells use phase separation and concentration gradients to organize chemical compartments inspace. Here, we present a theoretical study of droplet dynamics in gradient systems. We derive thecorresponding growth law of droplets andfind that droplets exhibit a drift velocity and positiondependent growth. As a consequence, the dissolution boundary moves through the system, therebysegregating droplets to one end. We show that for steep enough gradients, the ripening leads to atransient arrest of droplet growth that is induced by a narrowing of the droplet size distribution.
Lee CF, 2016, Interface stability, interface fluctuations, and the Gibbs-Thomson relation in motility-induced phase separations, Soft Matter, Vol: 13, Pages: 376-385, ISSN: 1744-6848
Minimal models of self-propelled particles with short-range volume exclusion interactions havebeen shown to exhibit signatures of phase separation. Here I show that the observed interfacial sta-bility and uctuations in motility-induced phase separations (MIPS) can be explained by modelingthe microscopic dynamics of the active particles in the interfacial region. In addition, I demon-strate the validity of the Gibbs-Thomson relation in MIPS, which provides a functional relationshipbetween the size of a condensed drop and its surrounding vapor concentration. As a result, the coars-ening dynamics of MIPS at vanishing supersaturation follows the classic Lifshitz-Slyozov scaling lawat the late stage.
Jean L, Lee CF, Hodder P, et al., 2016, Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide, Scientific Reports, Vol: 6, ISSN: 2045-2322
Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions.
Lee C, Chen L, Toner J, 2016, Mapping two-dimensional polar active fluids to two-dimensional soap and one-dimensional sandblasting, Nature Communications, Vol: 7, ISSN: 2041-1723
Active fluids and growing interfaces are two well-studied but very different non-equilibrium systems. Each exhibits non-equilibrium behaviour distinct from that of their equilibrium counterparts. Here we demonstrate a surprising connection between these two: the ordered phase of incompressible polar active fluids in two spatial dimensions without momentum conservation, and growing one-dimensional interfaces (that is, the 1+1-dimensional Kardar–Parisi–Zhang equation), in fact belong to the same universality class. This universality class also includes two equilibrium systems: two-dimensional smectic liquid crystals, and a peculiar kind of constrained two-dimensional ferromagnet. We use these connections to show that two-dimensional incompressible flocks are robust against fluctuations, and exhibit universal long-ranged, anisotropic spatio-temporal correlations of those fluctuations. We also thereby determine the exact values of the anisotropy exponent ζ and the roughness exponents χx,y that characterize these correlations.
Lee CF, Pruessner G, 2016, Percolation mechanism drives actin gels to the critically connected state, Physical Review E, Vol: 93, ISSN: 1539-3755
Cell motility and tissue morphogenesis depend crucially on the dynamic remodelling of actomyosinnetworks. An actomyosin network consists of an actin polymer network connected by crosslinkerproteins and motor protein myosins that generate internal stresses on the network. A recent discoveryshows that for a range of experimental parameters, actomyosin networks contract to clusterswith a power-law size distribution [Alvarado J. et al. (2013) Nature Physics 9 591]. Here, weargue that actomyosin networks can exhibit robust critical signature without fine-tuning becausethe dynamics of the system can be mapped onto a modified version of percolation with trapping(PT), which is known to show critical behaviour belonging to the static percolation universalityclass without the need of fine-tuning of a control parameter. We further employ our PT model togenerate experimentally testable predictions.
Pruessner G, Lee CF, 2016, Comment on "Anomalous Discontinuity at the Percolation Critical Point of Active Gels", Physical Review Letters, Vol: 116, ISSN: 1079-7114
Fan Lee C, 2015, Thermal breakage of a semiflexible polymer: breakage profile and rate, Journal of Physics: Condensed Matter, Vol: 27, ISSN: 0953-8984
Understanding fluctuation-induced breakages in polymers has important implications for basic and applied sciences. Here I present for the first time an analytical treatment of the thermal breakage problem of a semi-flexible polymer model that is asymptotically exact in the low temperature and high friction limits. Specifically, I provide analytical expressions for the breakage propensity and rate, and discuss the generalities of the results and their relevance to biopolymers. This work is fundamental to our understanding of the kinetics of living polymerisation.
Chen L, Toner J, Lee CF, 2015, Critical phenomenon of the order-disorder transition in incompressible active fluids, New Journal of Physics, Vol: 17, ISSN: 1367-2630
We study incompressible systems of motile particles with alignment interactions. Unlike their compressible counterparts, in which the order-disorder (i.e., moving to static) transition, tuned by either noise or number density, is discontinuous, in incompressible systems this transition can be continuous, and belongs to a new universality class. We calculate the critical exponents to $\mathcal{O}(\epsilon )$ in an $\epsilon =4-d$ expansion, and derive two exact scaling relations. This is the first analytic treatment of a phase transition in a new universality class in an active system.
Sartori P, Granger L, Lee CF, et al., 2014, Thermodynamic costs of information processing in sensory adaptation, PLoS Computational Biology, Vol: 10, ISSN: 1553-734X
Peng T, Paramelle D, Sana B, et al., 2014, Designing Non-Native Iron-Binding Site on a Protein Cage for Biological Synthesis of Nanoparticles, SMALL, Vol: 10, Pages: 3131-3138, ISSN: 1613-6810
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