Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Scaling Concepts in Serpin Polymer Physics.

ABSTRACT: α1-Antitrypsin is a protease inhibitor belonging to the serpin family. Serpin polymerisation is at the core of a class of genetic conformational diseases called serpinopathies. These polymers are known to be unbranched, flexible, and heterogeneous in size with a beads-on-a-string appearance viewed by negative stain electron microscopy. Here, we use atomic force microscopy and time-lapse dynamic light scattering to measure polymer size and shape for wild-type (M) and Glu342→Lys (Z) α1-antitrypsin, the most common variant that leads to severe pathological deficiency. Our data for small polymers deposited onto mica and in solution reveal a power law relation between the polymer size, namely the end-to-end distance or the hydrodynamic radius, and the polymer mass, proportional to the contour length. We use the scaling concepts of polymer physics to assess that α1-antitrypsin polymers are random linear chains with a low persistence length.

SUBMITTER: Raccosta S

PROVIDER: S-EPMC8156723 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-02-12 | GSE92294 | GEO

Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture (human)

Project description:Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and consecutive disease. However, the prediction of such effects remains a challenge. Here we present a polymer physics based approach (PRISMR) to model chromatin folding and to predict enhancer-promoter contacts. Using the Epha4 locus as a model, the effects of pathogenic SVs were predicted in-silico and compared to published Hi-C and capture Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolutes the folding complexity of the studied locus, and identifies SV-induced alterations of 3D genome organization in the homozygous as well as the heterozygous state. Our method accurately predicts the specific sites of ectopic chromatin contacts that produce extensive rewiring of regulatory interactions, causing disease by gene misexpression. PRISMR can be used to predict interactions in silico thereby providing a tool for analyzing the disease causing potential of SVs.

2018-02-12 | GSE92290 | GEO

Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture (mouse)

2018-02-12 | GSE92291 | GEO

Lithography of Polymer Nanostructures on Glass for Teaching Polymer Chemistry and Physics.

Project description:As nanolithography becomes increasingly important in technology and daily life, a variety of inexpensive and creative methods toward communicating the concepts underpinning these processes in the classroom are necessary. An experiment is described that uses simple CD-Rs, C-clamps, an oven, and a freezer to provide concrete examples and insights into the chemistry and principles of nanolithography. The experiment also has flexibility, making it suitable for a range of classroom levels from high school to more advanced labs in college. Because CD-Rs are composed of grooves of polycarbonate, the experiment provides a basis for discussions and exploration into the chemistry and physics of polymers on the nanoscale.

| S-EPMC3115560 | biostudies-literature

Polymer physics of chromosome large-scale 3D organisation.

Project description:Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

| S-EPMC4942835 | biostudies-literature

Scaling Laws in Supramolecular Polymer Networks.

Project description:The linear rheological properties of networks formed by adding bis-Pd(II) cross-linkers to poly(4-vinylpyridine) (PVP) solution are examined, and the scaling law relationships between the zero shear viscosity (?(0)) of the networks versus the concentration of PVP solution (C(PVP)), the concentration of cross-linkers (C(X)), and the number density of elastically active chains (v(phantom)) are experimentally determined. The scaling law relationships are compared to the theoretical expectations of the Sticky Rouse and Sticky Reptation models (Macromolecules2001, 34, 1058-1068), and both qualitative and quantitative differences are observed.

| S-EPMC3135979 | biostudies-literature

The biology and polymer physics underlying large-scale chromosome organization.

Project description:Chromosome large-scale organization is a beautiful example of the interplay between physics and biology. DNA molecules are polymers and thus belong to the class of molecules for which physicists have developed models and formulated testable hypotheses to understand their arrangement and dynamic properties in solution, based on the principles of polymer physics. Biologists documented and discovered the biochemical basis for the structure, function and dynamic spatial organization of chromosomes in cells. The underlying principles of chromosome organization have recently been revealed in unprecedented detail using high-resolution chromosome capture technology that can simultaneously detect chromosome contact sites throughout the genome. These independent lines of investigation have now converged on a model in which DNA loops, generated by the loop extrusion mechanism, are the basic organizational and functional units of the chromosome.

| S-EPMC5846894 | biostudies-literature

Models of polymer physics for the architecture of the cell nucleus.

Project description:The depth and complexity of data now available on chromosome 3D architecture, derived by new technologies such as Hi-C, have triggered the development of models based on polymer physics to explain the observed patterns and the underlying molecular folding mechanisms. Here, we give an overview of some of the ideas and models from physics introduced to date, along with their progresses and limitations in the description of experimental data. In particular, we focus on the Strings&Binders and the Loop Extrusion model of chromatin architecture. This article is categorized under: Analytical and Computational Methods > Computational Methods.

| S-EPMC6565494 | biostudies-literature

Effective concentrations enforced by intrinsically disordered linkers are governed by polymer physics.

Project description:Many multidomain proteins contain disordered linkers that regulate interdomain contacts, and thus the effective concentrations that govern intramolecular reactions. Effective concentrations are rarely measured experimentally, and therefore little is known about how they relate to linker architecture. We have directly measured the effective concentrations enforced by disordered protein linkers using a fluorescent biosensor. We show that effective concentrations follow simple geometric models based on polymer physics, offering an indirect method to probe the structural properties of the linker. The compaction of the disordered linker depends not only on net charge, but also on the type of charged residues. In contrast to theoretical predictions, we found that polyampholyte linkers can contract to similar dimensions as globular proteins. Hydrophobicity has little effect in itself, but aromatic residues lead to strong compaction, likely through ?-interactions. Finally, we find that the individual contributors to chain compaction are not additive. We thus demonstrate that direct measurement of effective concentrations can be used in systematic studies of the relationship between sequence and structure of intrinsically disordered proteins. A quantitative understanding of the relationship between effective concentration and linker sequence will be crucial for understanding disorder-based allosteric regulation in multidomain proteins.

| S-EPMC6859346 | biostudies-literature

Distinct polymer physics principles govern chromatin dynamics in mouse and Drosophila topological domains.

Project description:BackgroundIn higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. While a crumpled/fractal globule organization has received experimental supports at higher-order levels, the organization principles that govern chromatin dynamics within these TADs remain unclear. Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.ResultsHere, we use data from diverse 3C-derived methods to explore chromatin dynamics within mouse and Drosophila TADs. In mouse Embryonic Stem Cells (mESC), that possess large TADs (median size of 840 kb), we show that the statistical helix model, but not globule models, is relevant not only in gene-rich TADs, but also in gene-poor and gene-desert TADs. Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells. Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization. In Drosophila, which possesses TADs of smaller sizes (median size of 70 kb), we show that, while chromatin compaction and flexibility are finely tuned according to the epigenetic landscape, chromatin dynamics within TADs is generally compatible with an unconstrained polymer configuration.ConclusionsModels issued from polymer physics can accurately describe the organization principles governing chromatin dynamics in both mouse and Drosophila TADs. However, constraints applied on this dynamics within mammalian TADs have a peculiar impact resulting in a statistical helix organization.

| S-EPMC4536789 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data