Biophysics Commons^™

Biophysical Insights Into Peptide And Alcohol Perturbations On Biomimetic Membranes, Michael Hai Nguen

Electronic Theses and Dissertations

Biological membranes exist in every domain of life. Life exists due to the presence of these special structures for which we take for granted. They are composed of fatty lipids and workhorse proteins and act as the premier interface of biological processes. Due to the sheer quantity and complexity within their thin boundary, studying their actions and properties pose challenges to researchers. As a result, simplified biomembrane mimics are employed regularly. We will use several types of biomembrane mimics to understand fundamental properties of membranes. In the present thesis, we also attempt to move beyond the canonical structure-based theories upon …

Deciphering Chemomechanical Couplings In Proteins Using Microsecond-Level Molecular Dynamics Simulations, Vivek Govind Kumar

Graduate Theses and Dissertations

All-atom molecular dynamics (MD) simulations combine the high temporal resolution of experimental methods like smFRET and spatial resolution of methods like x-ray crystallography, to provide a detailed dynamic picture of biomolecular processes. Here, microsecond-level atomistic MD simulations have been used to characterize chemomechanical couplings in human fibroblast growth factor 1 (hFGF1) and the spike proteins of SARS CoV-1 and SARS-CoV-2. hFGF1 is a globular signaling protein that is involved in several physiological processes ranging from cell proliferation to wound healing. Experimental studies have previously described the low proteolytic and thermal stability of hFGF1, in addition to the stabilizing role of …

Understanding The Relationship Between Local Environmental Changes And The Function Of The Ph Low Insertion Peptide, Violetta Burns Casamayor

Graduate Theses, Dissertations, and Problem Reports

Cancer is the second leading cause of death in the US with over 1.7 million new cases each year. Current cancer treatments tend to also target healthy tissues due to similarities with cancerous ones, resulting in acute side effects. Early detection is the best approach towards defeating cancer, however, modern imaging techniques require sizeable samples, often implying a late stage in the disease. One common attribute of tumors is their acidic microenvironment, which can be taken advantage of.

The pH Low Insertion Peptide (pHLIP) is a membrane-active peptide that can take advantage of the acidic microenvironment surrounding cancer cells. pHLIP …

Modeling Mechanisms Behind Force Generation By Actin Polymerization, Seyed Fowad Motahari

Arts & Sciences Electronic Theses and Dissertations

Actin polymerization is the primary mechanism for overcoming the large turgor pressure that opposes endocytosis in yeast. While generation of pushing forces by actin polymerization is fairly well understood, it is not clear how actin polymerization produces pulling forces. In order to understand this process, it is necessary to simulate polymerization of filaments having various types of interactions with the membrane. Since existing methodologies in the literature do not treat such problems correctly, we develop a thermodynamically consistent methodology for treating polymerization of filaments having arbitrary interaction potentials with the membrane. Then I perform stochastic simulations for a system of …

Molecular Mechanism Of Early Amyloid Self-Assembly Revealed By Computational Modeling, Mohtadin Hashemi

Theses & Dissertations

Protein misfolding followed by the formation of aggregates, is an early step in the cascade of conformational changes in a protein that underlie the development of several neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. Efforts aimed at understanding this process have produced little clarity and the mechanism remains elusive.

Here, we demonstrate that the hairpin fold, a structure found in the early folding intermediates of amyloid b, induces morphological and stability changes in the aggregates of Aβ(14-23) peptide. We structurally characterized the interactions of monomer and hairpin using extended molecular dynamics (MD) simulations, which revealed a novel intercalated type complex. …

Dynamic Control Of Particle Separation In Deterministic Lateral Displacement Separator With Viscoelastic Fluids, Yuke Li, Hongna Zhang, Yongyao Li, Xiaobin Li, Jian Wu, Shizhi Qian, Fengchen Li

Mechanical & Aerospace Engineering Faculty Publications

We proposed an innovative method to achieve dynamic control of particle separation by employing viscoelastic fluids in deterministic lateral displacement (DLD) arrays. The effects of shear-thinning and elasticity of working fluids on the critical separation size in DLD arrays are investigated. It is observed that each effect can lead to the variation of the critical separation size by approximately 40%. Since the elasticity strength of the fluid is related to the shear rate, the dynamic control can for the first time be easily realized through tuning the flow rate in microchannels.

Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse

Arts & Sciences Electronic Theses and Dissertations

Intrinsically disordered proteins and protein regions (IDPs) represent around thirty percent of the eukaryotic proteome. IDPs do not fold into a set three dimensional structure, but instead exist in an ensemble of inter-converting states. Despite being disordered, IDPs are decidedly not random; well-defined - albeit transient - local and long-range interactions give rise to an ensemble with distinct statistical biases over many length-scales. Among a variety of cellular roles, IDPs drive and modulate the formation of phase separated intracellular condensates, non-stoichiometric assemblies of protein and nucleic acid that serve many functions. In this work, we have explored how the amino …

Structural Adaptations Of Proteins To Different Biological Membranes, Prof. Stephanie Tristram-Nagle, Irina Pogozheva, Harold Mosberg, Andrei Lomize

Prof. Stephanie Tristram-Nagle Ph.D.

To gain insight into adaptations of proteins to their membranes, intrinsic hydrophobic thicknesses, distributions of different chemical groups and profiles of hydrogen-bonding capacities (α and β) and the dipolarity/ polarizability parameter (π*) were calculated for lipid-facing surfaces of 460 integral α-helical, β-barrel and peripheral proteins from eight types of biomembranes. For comparison, polarity profiles were also calculated for ten artificial lipid bilayers that have been previously studied by neutron and X-ray scattering. Estimated hydrophobic thicknesses are 30–31 Å for proteins from endoplasmic reticulum, thylakoid, and various bacterial plasma membranes, but differ for proteins from outer bacterial, inner mitochondrial and eukaryotic …