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Articles 1 - 11 of 11
Full-Text Articles in Biological Engineering
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Doctoral Dissertations
The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …
Surface Enhanced Raman Spectroscopy (Sers) As An Approach For The Emerging Liquid Biopsy Diagnostics, Nariman Banaei
Surface Enhanced Raman Spectroscopy (Sers) As An Approach For The Emerging Liquid Biopsy Diagnostics, Nariman Banaei
Doctoral Dissertations
Large Molecule bioanalysis and biosensor development are essential techniques that are required in many applications, including biotherapeutic development, in vitro diagnostic, biomarker detection, and early detection. These techniques should be highly specific and sensitive enough to identify and quantify an analyte of interest with minimum sample pretreatment requirements. This work explores the development and application of chip-scale bioassays based on surface-enhanced Raman scattering (SERS). It introduces sensing techniques to quantify various disease biomarkers, specifically pancreatic cancer. Blood is the best source of information about our body's function. There are many biomarkers in the blood, and each biomarker's high expression level …
Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma
Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma
Doctoral Dissertations
The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …
Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois
Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois
Doctoral Dissertations
Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …
From Soap Bubbles To Cell Membranes, Peter Beltramo
From Soap Bubbles To Cell Membranes, Peter Beltramo
Science and Engineering Saturday Seminars
Have you ever blown a soap bubble and wondered - what causes the bubble to be so stable and produces those colorful reflections of light? The answer lies in a class of molecules known as surfactants, and they have remarkable similarities with the molecules that comprise the cell membrane of all living organisms. In this workshop, we will use the analogy of a soap bubble to describe cellular membrane properties such as chemistry, structure, membrane transport, and ion channel formation. The goals of this workshop are to 1) link initially intractable concepts in biology like intracellular transport to the intuitive …
Building The Outer Membrane Protein G (Ompg) Nanopore Library: From The Discrimination Of Biotin-Binding Proteins In Serum To Resolving Human Carbonic Anhydrase From Human Red Blood Cells, Bib Yang
Doctoral Dissertations
The use of pore-forming proteins (PFPs) in nanopore sensing has been fruitful largely due to their nanoscale size and the ease with which protein nanopores can be manipulated and consistently reproduced at a large scale. Nanopore sensing relies heavily on a steady ionic current afforded by rigid nanopores, as the change in current is indicative of analyte detection, revealing characteristics of the analyte such as its relative size, concentration, and charge, as well as the nanopore:analyte interaction. Rigid PFPs have been used in applications such as DNA sequencing, kinetic studies, analyte discrimination, and protein conformation dynamics at the single-molecule level. …
Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz
Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz
Doctoral Dissertations
Breast cancer is plagued by two key clinical challenges; drug resistance and metastasis. Most work to date probes these events on an extremely rigid plastic surface, which recapitulates few aspects of these processes in humans. A malignant cell first resides in breast tissue, then likely travels to the bone, brain, liver, or lung, each of which has a distinct mechanical and biochemical profile. Cells transmit mechanical forces into intracellular tension and biochemical signaling events, and here we hypothesize that this mechanotransduction influences drug response, growth, and migration. To probe the impact of extracellular matrix on drug resistance, we defined a …
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Doctoral Dissertations
The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …
Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney
Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney
Doctoral Dissertations
To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …
Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen
Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen
Doctoral Dissertations
The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …
The Discovery And Study Of Fluvirucin B1 Polyketide Synthase, Tsung-Yi Lin
The Discovery And Study Of Fluvirucin B1 Polyketide Synthase, Tsung-Yi Lin
Doctoral Dissertations
Rapidly decreasing numbers of viable therapeutic leads in the pharmaceutical pipeline demand new, sustainable methods for improved drug discovery and development. Despite vast improvements in de novo drug design and target recognition, Nature remains the richest source of small molecule therapeutics. Among many natural products, polyketides are not only the most promising ones for developing new antibiotic leads, but also exhibit unusually high therapeutic value ranging from clinical use as anticancer, antiviral, and immunosuppressant drugs. Modular polyketide synthases (PKSs) are dedicated nano-machinery that can be manipulated to produce a structurally diverse library for drug discovery programs. The ability to manipulate …