Engineering Commons^™

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Representation Learning For Chemical Activity Predictions, Mohamed S. Ayed

Dissertations, Theses, and Capstone Projects

Computational prediction of a phenotypic response upon the chemical perturbation on a biological system plays an important role in drug discovery and many other applications. Chemical fingerprints derived from chemical structures are a widely used feature to build machine learning models. However, the fingerprints ignore the biological context, thus, they suffer from several problems such as the activity cliff and curse of dimensionality. Fundamentally, the chemical modulation of biological activities is a multi-scale process. It is the genome-wide chemical-target interactions that modulate chemical phenotypic responses. Thus, the genome-scale chemical-target interaction profile will more directly correlate with in vitro and in …

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Mutagenesis Of Human Alpha-Galactosidase A For The Treatment Of Fabry Disease, Erin Stokes

Dissertations, Theses, and Capstone Projects

Fabry disease is an X-linked lysosomal storage disorder caused by the deficiency of the enzyme, α-galactosidase A, which results in the accumulation of the lipid substrate. This accumulation results in obstruction of blood flow in patients and early demise at approximately 40-60 years of age. There is currently only one FDA approved treatment (Fabrazyme) classified as an enzyme replacement therapy. However, approximately 88% of patients experience a severe immune response that, rarely, can be fatal and is a huge cost burden at average $250,000 a year per patient. The structure of α-galactosidase A has been previously determined to be a …

Mechanotransduction Modulates The Effect Of Mechanical Forces (Fluid Shear Stress And Cyclic Strain) On Embryonic Stem Cell Differentiation Toward Vascular Endothelial Cells, Maria Nikmanesh

Dissertations, Theses, and Capstone Projects

The isolation of human ES cells (hES) in 1998 remarkably elevated the interest in the cell therapy capability of ES cells and moved this concept one step closer to reality. Embryonic stem cells with their potential for both self-renewal and directed differentiation have received increasing attention in applications in tissue engineering and repair, cell therapy, and regenerative medicine.

The differentiation of embryonic stem cells into desired lineages depends on the chemical environment of the “niche”, and for certain lineages such as the vascular lineage that must function in a mechanical environment, the timely imposition of mechanical forces is critical. In …

Effect Of Temporal Onset Of Mechanical Loading On Tendon To Bone Healing, Determined With A Novel In-Vivo Device, Mark E. Stasiak

Dissertations, Theses, and Capstone Projects

Background: Exposure to tensile loading has been shown to maintain tendon/ligament homeostasis, with the tensile modulus of the tissue increasing in response to greater loading frequency, and even decreasing in the absence of load. However after injury or surgical repair the effect of tensile load is controversial, with many studies implicating mechanical loading with impaired healing. It is currently unknown when the tensile loading imparted during rehabilitation exercise, can be safely reintroduced after surgical tendon repair or ligament reconstruction, and at what time point it can most benefit the remodeling process. To investigate the effect of tensile loading protocols on …