Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session G18: BiopolymersFocus Recordings Available
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Sponsoring Units: DPOLY DSOFT DBIO Chair: Andy Spakowitz, Stanford University Room: McCormick Place W-184D |
Tuesday, March 15, 2022 11:30AM - 12:06PM |
G18.00001: Assessing Protein Corona Formation on Hard and Polymeric Nanoparticles – Towards Understanding Biocompatibility, Biodistribution, and Efficacy Invited Speaker: Markita P Landry Unpredictable protein adsorption on both hard and soft nanoparticles remains a considerable challenge towards effectively applying nanotechnologies in biological environments. Hard nanoparticles form the basis of many chemical nanosensors. Conversely, soft nanoparticles such as lipid nanoparticles (LNPs) are vital for the successful delivery of mRNA-based vaccines, and offer promising applications in immunotherapy and protein replacement therapy. Herein, we present a multimodal study of protein corona composition and dynamics, first on ‘hard’ nanoparticles: spherical polystyrene nanoparticles and high aspect ratio single-walled carbon nanotubes (SWCNTs). These nanoparticles are exposed to two biofluids of interest: blood plasma (relevant for intravenous applications) and cerebrospinal fluid (relevant for brain imaging and sensing applications). While polystyrene nanoparticles are relatively agnostic in the formation of their protein coronas, SWCNTs show strong preference for certain protein classes. Our analysis shows that corona compositions, and more broadly nanoparticle biofouling, can be drastically different for each nanoparticle type. |
Tuesday, March 15, 2022 12:06PM - 12:18PM |
G18.00002: Human Airway Mucus: Cactus-like Conformations of Associative Polymers Scott Danielsen, Michael Rubinstein The unique fractal structure of macromolecules in human bronchial epithelial mucus is determined by small-angle neutron scattering. Hybrid Monte Carlo/molecular dynamics simulations of a minimal coarse-grained model of polymers with associative groups distributed evenly along the chain contour is found to reproduce the experimental form factor. A unique "cactus" model resulting from loops of different orders is proposed. Predictions with number and spacing between associative groups are given for the scaling of the polymer radius of gyration, contact probability, and pairwise interchain interactions. |
Tuesday, March 15, 2022 12:18PM - 12:30PM |
G18.00003: Role of Active and Thermal Fluctuations in Biopolymer Dynamics Ashesh Ghosh, Andrew J Spakowitz Life maintains itself as an out of equilibrium phenomenon and poses a fundamental difficulty in biological physics in establishing a predictive time-dependent statistical mechanical theoretical understanding. We develop a theoretical framework for predicting the combined influence of active and Brownian forces in biopolymer dynamics. The active forces exhibit a temporal correlation in their statistical behavior, capturing the processivity associated with the characteristic time scale of biological fluctuations such as enzymatic activity. Based on a path-integral formalism, we demonstrate that the non-equilibrium fluctuations can be mapped onto an “effective” time-dependent temperature that depends on active-force statistics. This theoretical picture suggests a hierarchy of length and timescale dependent behaviors, where local conformational fluctuations are unaffected by the presence of active forces, but large length-scale conformational dynamics are significantly altered. These results suggest that active fluctuations have a varying impact on biological events based on the time and length scale of information processivity. Furthermore, the concept of a time-dependent temperature provides a roadmap for the interpretation of in vivo measurements across wide observation timescales. |
Tuesday, March 15, 2022 12:30PM - 12:42PM |
G18.00004: A mean-field theory to predict statistics of semiflexible biomolecules due to inhomogeneous forces Ananya Mondal, Greg Morrison Biomolecules such as DNA perform key roles governed by their mechanical responses to tensile forces exerted by other biomolecules in vivo. Single-molecule force-extension experiments help us to study the mechanical responses of biopolymers to applied forces such as electrophoretic stretching in microfluidic devices used for DNA sequencing. The effects of inhomogeneous tension on the extension of charged biopolymers under electric fields are not well understood. In our work, we modify an existing analytically tractable mean-field approach to account for the heterogeneity in tension for electric fields. This model has been shown to successfully predict the force-extension relations of inextensible polymers under uniform tension. However, for non-uniform stretching, naively using this model results in local overstretching of the polymer under an electric field. So, we improve this approach by subdividing the chain into smaller segments while imposing the inextensibility of the chain and eventually predicting experimentally relevant observables like force-extension relations and fluctuations for non-uniform forces. The proposed method may be applied to the study of the extension of DNA in confined nanochannels and protein-DNA packaging statistics. |
Tuesday, March 15, 2022 12:42PM - 12:54PM |
G18.00005: Nanopore Chip with Self-Aligned Transverse Tunneling Junction for Biomolecule Detection and Sequencing Sanjana Mukherjee, Yuan Wang, Joshua S Sadar, Ching-Wei Tsao, Quan Qing There is an urgent need for a technique to directly sequence DNA/RNA with chemical specificity and accuracy for detection at single-molecule level. Solid-state nanopore technology has the potential of having tunneling electrodes as a new readout mechanism for higher resolution detection. However, fabrication of such structures has been extremely challenging. Here we report a new strategy for fabricating a solid-state nanopore with transverse tunneling junction integrated inside a nanofluidic channel, where DNA molecules can be enriched and straightened to pass through the nanopore between the electrodes. The nanopore size is then reversibly tuned through a controlled electrochemical process in real time. We have successfully shown that coincidental ionic and tunneling signals can be reproducibly detected for DNA translocation events with >93% yield. We have also observed events related to DNA bridging the transverse electrodes, which showed different amplitude and duration distribution compared to translocating events. With additional optimization of multiplexed detection and translocation control, our design can be further developed into a low-cost platform for single biomolecule delivery, manipulation, detection and sequencing. |
Tuesday, March 15, 2022 12:54PM - 1:06PM |
G18.00006: Unexpected fluorescence in peptide amphiphile micelles for molecular-recognition sensing applications Whitney C Fowler Intrinsically fluorescent soft materials have been widely studied for their signaling applications. A class of fluorescent materials of recent interest are aggregation-induced emission (AIE) materials, which consist of molecules which only fluoresce when assembled into a larger construct. However, the mechanism of AIE is poorly understood, and the materials are often poorly soluble in water, hard to synthesize, and difficult to functionalize, which limits their potential for mechanistic study and real-world impact. Interestingly, I recently discovered that peptide amphiphile (PA) micelles fluoresce without individually fluorescent subunits or aromatic rings, revealing a new class of AIE materials not previously studied. Peptide amphiphiles consist of a functional peptide headgroup conjugated to a hydrophobic tail that spontaneously self-assemble in water. They are water-soluble and easy to straightforwardly functionalize using well-controlled sequence-specific synthesis. Moreover, preliminary results indicate that fluorescence is quenched when the PA micelles bind to phosphate, presenting a promising and readily tunable platform for mechanistic study and sensing applications. This work will present the design, characterization, and functionality of this newly discovered and versatile AIE material. |
Tuesday, March 15, 2022 1:06PM - 1:18PM |
G18.00007: Bayesian Inference of Chromatin Looping Simon B Grosse-Holz, Hugo B Brandão, Michele Gabriele, Asmita Jha, Claudia Cattoglio, Tsung-Han S Hsieh, Leonid A Mirny, Christoph Zechner, Anders S Hansen With the advent of new imaging technologies, we are increasingly able to observe the highly dynamic organization of chromatin in real time. An especially interesting class of experiments being developed in several groups tracks two genomic loci on the same chromosome, in the hope of gaining mechanistic insight into the mechanisms underlying their interaction. Specifically the formation of chromatin loops by a mechanism known as loop extrusion is assumed to be a central motif in the regulation of genome structure. We developed a Bayesian inference algorithm to detect sustained contacts in two-particle tracking experiments, thereby uncovering the dynamics of chromatin loops. While the biological insight from this application alone is considerable, the algorithm itself is very general and is immediately applicable to other experiments, e.g. to study the interaction of enhancers and promoters. |
Tuesday, March 15, 2022 1:18PM - 1:30PM |
G18.00008: Extreme elastic properties of mechanosensory chordotonal organs in Drosophila Xiaoxuan Jian, Chonglin Guan, Kengo Nishi, Christian Kreis, Oliver Baeumchen, Martin C Göpfert, Christoph F Schmidt Mechanosensory organs in higher organisms, especially propiosensory organs that monitor body movements, are often pre-strained. This allows the organs to adapt to body motions and maintain sensitivity. Some of the tension regulation typically is part of active feedback mechanisms, but it appears that there also are mechanisms that generate persistent prestrain and the corresponding pretension in tissues. How this occurs and how it is regulated, is not understood. Here we study the lateral pentascolopidial organ (lch5), a type of chordotonal organ (ChO), of Drosophila larvae. This organ is a propioceptor constructed as an axial tension sensor that responds to tension changes between two anchoring points in the larval cuticle during body muscle contractions. We performed micromanipulation experiments using glass microneedles to probe the lch5 organ mechanics with calibrated forces. We found that ChO cap cells display extreme elastic properties that create a 400% dynamic range of strain. Furthermore, we show that the extracellular matrix (ECM) surrounding the cap cells is responsible for maintaining the pretension and elasticity of ChOs. |
Tuesday, March 15, 2022 1:30PM - 1:42PM |
G18.00009: A coarse-grain elastic lattice polymer model of bacterial chromosomes Elham Ghobadpour, Ralf Everaers, Ivan Junier Supercoiled DNA, often adopt tree-like double-folded, randomly branching configurations. In this context, we studied an elastic lattice polymer model for tightly double-folded ring polymers. This model includes the spontaneous creation and deletion of side branches, which move along the tree graph structure due to local mass transport diffusion. We used Monte Carlo simulations to study systems falling into different universality classes: ideal double-folded rings without excluded volume interactions, self-avoiding double-folded rings, and double-folded rings in the melt state. The static properties are in good agreement with exact results, simulations, and predictions of Flory theory. For example, in the melt state rings adopt compact configurations and exhibit territorial behavior. In particular, we show that the emergent dynamics is in excellent agreement with a recent scaling theory. |
Tuesday, March 15, 2022 1:42PM - 1:54PM |
G18.00010: Modulation of DNA entanglements by Nucleoid Associated Proteins Davide Michieletto The bacterial genome can be up to ~mm-long when stretched and yet is packaged within a ~um-size cell. Its correct folding and organization are vital as entanglements between DNA segments are detrimental and may lead to cell death. Much of this organization is due to abundant Nucleoid Associated Proteins (NAPs). In spite of our understanding of the detailed molecular details through which NAPs bend, kink, coat, stiffen and bridge bacterial genomes, the precise mechanisms through which they organize bacterial genomes in dense and crowded environments remains elusive. The Integration Host Factor (IHF) and Histone-like Nucleoid-Structuring (HNS) proteins are examples of abundant NAPs that organize the bacterial genome. While the former kinks DNA at extreme angles, the latter can either stiffen or bridge DNA depending on pH, temperature, or concentration of divalent ions. In this talk, I will report on recent results we obtained using particle tracking microrheology on entangled solutions of large lambda-DNA functionalized by IHF/HNS proteins. We show that IHF can strongly reduce entanglements and even remove elastic components ultimately fluidizing the solution of entangled DNA. At the same time, we observe that in spite of its role to stiffen and bridge DNA molecules, HNS has only a moderate impact in increasing the fluid viscosity and elasticity. Taken together our results suggest that while IHF may be essential to "fluidize" the bacterial genome, HNS may be employed to silence genes locally without introducing long-lived entanglements which may negatively impact cell health. |
Tuesday, March 15, 2022 1:54PM - 2:06PM |
G18.00011: Mechanical Properties Of Peptide Nucleic Acids Khadka B Chhetri, Akshara B Sharama, Supriyo B Naskar, Prabal K Maiti Peptide nucleic acids (PNA) are charge neutral polyamide oligomers, having high thermal endurance and high stability inside cells. We studied the microscopic structures and elastic properties of double-stranded PNA (dsPNA) and their hybrid derivatives using all-atom MD simulation and compared them with double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA). The stretch modulus of the dsPNA is found to be ~160 pN, an order of magnitude lower than that of dsDNA and dsRNA. Similarly, the persistence length of dsPNA is found to be ~37 nm, significantly smaller than those of dsDNA and dsRNA. The PNA-DNA and PNA-RNA hybrid duplexes have elastic properties lying between that of dsPNA and dsDNA/dsRNA. We argue that the neutral backbones of the PNA make it less stiff than dsDNA and dsRNA. Measurement of structural crookedness and principal component analysis additionally support the bending flexibility of dsPNA. Detailed analysis of the helical-rise coupled to helical-twist indicates that PNA-DNA hybrid over-winds like dsDNA, while PNA-PNA and PNA-RNA unwind like dsRNA upon stretching. Because of the highly flexible nature of PNA, it can bind other biomolecules by adapting a wide range of conformations and is believed to be crucial for future nanobiotechnology researches. |
Tuesday, March 15, 2022 2:06PM - 2:18PM |
G18.00012: Stochastic dynamics of coupled DNA loci on a compacted chromosome David B Brückner, Lev Barinov, Hongtao Chen, Thomas Gregor Chromosomes are highly compacted and organized to fit into the eukaryotic nucleus. For many functional processes, including the initiation of transcription, pair-wise interactions of distal chromosomal elements, such as enhancers and promoters, are essential. Previous theory based on simple polymer models successfully captures the dynamics of single DNA loci in terms of sub-diffusive motion in the viscoelastic nucleoplasm. However, how these approaches extend to the joint motion of pairs of DNA loci remains unclear. Using a live imaging assay to simultaneously measure positions of pairs of enhancers and promoters in thousands of nuclei of the developing fly embryo, we analyze the two-point correlations of these DNA loci. Our analysis reveals long-ranged correlations with striking deviation from simple polymer models. We show how these findings are related to the compaction of the chromosome, highlighting the key role of spatial chromosome organization in determining the coupled dynamics of DNA loci. |
Tuesday, March 15, 2022 2:18PM - 2:30PM |
G18.00013: Dynamic bridging explains sub-diffusive movement of chromosomal loci Srikanth Subramanian, Sean Murray Chromosomal loci in bacterial cells show a robust sub-diffusive scaling of the mean square displacement (MSD)~ τ0.4 under various growth conditions and antibiotic treatments. Recent experiments have also shown that DNA-bridging Nucleoid Associated Proteins (NAPs) play an important role in chromosome organization and compaction. Here, using polymer simulations we investigate the role of DNA bridging in determining the dynamics of chromosomal loci. We find that bridging compacts the polymer and reproduces the sub-diffusive dynamics of monomers at timescales shorter than the bridge lifetime. Furthermore, the measured scaling exponent defines a relationship between chromosome compaction and bridge lifetime. Based on the observed mobility of chromosomal loci, we predict a lower bound on the average bridge lifetime of ~ 9 seconds. Finally, we show how bridging influences the average mesh size of the polymer, an experimentally measurable quantity. |
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