Summer 2024 Project Descriptions

Nanobiotechnology

Reinemann Lab: The Molecular Biophysics and Engineering Lab develops new approaches to study cytoskeletal mechanics that are important for vital life tasks, such as cell division and cell motility. Actin and microtubule (MT) cytoskeletal systems are vital for cell proliferation but are typically studied as separate entities. Communication between these disparate systems begins at the nanoscale through motor proteins and crosslinkers and propagates throughout the cytoskeleton. However, the mechanisms that facilitate crosstalk are not understood. In addition, there is growing evidence that when cytoskeletal proteins work in groups, they have emergent properties that are not necessarily the sum of their constituent single molecules. Under the guidance of Dr. Reinemann and a graduate student mentor, the REU student will study the mechanics of this emergent cytoskeletal crosstalk through engineering protein elements into synthetic “nanocells”, or nanoscale structures that mimic the cell’s structural hierarchy, using optical tweezers (OT), fluorescence microscopy, and a quartz crystal microbalance with dissipation monitoring (QCM-D). The REU student will first learn basic bench work techniques and building in vitro microscopy assays using flow cells. To verify polymerization of actin and MTs, the student will visualize the filaments on the OT microscope in fluorescence mode. This is also an excellent experience for learning how to make a microscopy sample, using the OT setup, getting samples in focus, and obtaining quality images. The student will construct an actin-MT nanocell, measure its mechanics using OT and QCM-D, and analyze data using Matlab. This project will help contribute to the lab’s understanding of how molecular-level crosstalk and coordination through inherently different cytoskeletal “beams,” crosslinkers, and “trusses” propagates up in scale to drive cellular processes necessary to sustain life.

Smith Lab: The Smith lab utilizes controlled radical polymerization (CRP) to synthesize stimuli-responsive block copolymers (BCPs) for the targeted delivery of nucleic acid (NA) therapeutics. The intravenous delivery of small interfering RNA (siRNA) is hampered by the rapid degradation of naked nucleic acids during circulation. As CRP techniques and facile conjugation chemistries have developed over the past two decades, polymer chemists now have tremendous control over polymer properties, enabling the rational design of polymeric NA delivery vehicles. Reversible addition-fragmentation chain transfer (RAFT) polymerization is arguably the most suitable CRP technique for preparing delivery vehicles for use in biological fluids.[50] Moreover, there is increasing interest in the controlled polymerization of monomers with latent reactive functionality, e.g. 2-vinyl-4,4-dimethylazlactone (VDMA), to modify the polymer or BCP. Such modifications enable synthesis of polymers with wide-ranging functionality from a single precursor, eliminating complications in synthesizing polymers of disparate functionality while maintaining constant polymer lengths. The REU student will synthesize BCPs of poly(ethylene glycol) (PEG) and VDMA. The synthesized BCPs will undergo post-polymerization modification with 2-(dimethylamino)ethanol and N,N-dimethylethylenediamine to yield BCPs with hydrolyzable, “charge reversing” side chains and analogous BCPs with hydrolytically-stable side cationic chains. The UG will characterize the BCPs via ¹H NMR spectroscopy and gel permeation chromatography to determine the composition, molecular weight, and polydispersity of the BCPs and utilize agarose gel electrophoresis, dynamic light scattering, and spectrophotometry to examine how BCPs form stable polyplexes with siRNA and protect the nucleic acid payload from nuclease degradation.

Tanner Lab: The Tanner lab seeks to solve outstanding bioengineering research questions using a chemistry framework, where an understanding of the molecular interactions within the delivery system allows the development of predictive frameworks and task-specific solvent design. Ionic liquids, consisting of a bulky, asymmetric cation and an anion, have attracted significant interest in a broad range of applications, including catalysis and energy applications, due to their favorable properties, including non-volatility, recyclability, and their inherent tuneability whereby the anion and cation can be altered to change the physicochemical properties of the material. A range of common cations and anions are shown in the picture to the right. By synthesizing the ionic liquids with biocompatible or bioinspired starting materials, they can be employed in biological contexts. Because changing the structure of the ionic components results in changes to their their biologically relevant properties, including interactions with bio-interfaces, biomolecules and pharmaceutical ingredients, they can be tuned to solve a variety of problems. 

Walker Lab: The Microdevices Lab uses micro- and nano-technology to address pressing needs in medicine and biology. The lab is working on developing an implantable drug delivery device that will treat depression, a condition with debilitating impact on millions of patients worldwide. The miniaturized biodegradable implant will ultimately contain dozens of doses of a drug that will be delivered every three to seven days and last for up to a year. The technology behind the device relies on dissolvable polymers, and the design challenge is to fabricate layers of appropriate thickness to control the rate of drug release. The microfabrication techniques required to make this device have not been fully developed, and the REU student who joins this project will assist in developing these new techniques and characterizing device performance. The student will learn the principles behind photolithography and micromolding and then iteratively fabricate devices to determine the appropriate process parameters for successfully fabricating a drug delivery device that can release drug intermittently. In the first set of experiments, the student will evaluate each device using both a stereoscope and scanning electron microscope to ensure appropriate dimensions and that the layers form sufficient seals. The student will evaluate device performance in a second set of experiments. The student will load devices with a fluorescent dye and then submerge them in saline. The release profile will be assessed by the periodic measurement of saline fluorescence. The student will correlate release performance with the measured dimensions and process parameters, providing crucial information to this project.

Werfel Lab: Cancer immunotherapies such as immune checkpoint inhibitors (ICIs) are revolutionizing cancer therapy. However, only a portion of patients benefit from ICIs and many patients cannot complete treatments due to severe, life-threatening side effects. Our lab develops polymeric nanoparticles which can encapsulate immunomodulatory agents and target the delivery of these agents to immune cells to boost immunogenicity and treatment responses. This work sits at the interface of nanotechnology and cancer immunology, leveraging approaches in nanoparticle synthesis, characterization, and drug delivery; nano-bio interactions; and cellular/molecular biology. The Werfel Lab will support one REU student to produce polymeric nanoparticles with “sheddable” coronas for improved targeting of tumor-specific innate immune cells. These nanoparticles will be composed of two BCPs – one with a glucopyranose-based corona which is shed in reducing environments (e.g. tumor microenvironment) to unveil a hidden targeting ligand, methacrylamidomannose for macrophage-specific targeting in tumors. The REU student will perform synthesis of the BCPs making up these nanoparticles, followed by characterization of the BCPs for molecular weight and composition via ¹H-NMR, GPC, and FT-IR. Next, the student will confirm that the glucopyranse polymer block (linked via a disulfide bond) can be removed in reducing conditions using glutathione and measuring polymer degradation by ¹H-NMR (to view compositional changes) and GPC (to view change in molecular weight). Lastly, the student will produce nanoparticles composed of both BCPs; characterize the size, morphology, and surface charge of the nanoparticles via light scattering and electron microscopy; and monitor the “shedding” of glucopyranose coronas by monitoring size and morphology changes upon addition of glutathione. These studies will position the REU student for a publication in a drug delivery-focused journal and position our research group to deliver tumor macrophage-specific therapies with improved therapeutic windows in future work.

 

Sustainable Nanoengineering

Alkhateb Lab: The NanoInfrastructure Research Laboratory (NIRL)’s goal is to understand the mechanics of nanomaterials in multi-scale contexts and to use them to improve the nation’s infrastructure. Specifically, NIRL uses computational and physical characterization approaches to develop and optimize novel graphene and polymer-based nanocomposites, such as nano-concrete and nano-asphalt, as well as materials for space applications, such as environmental coatings for the International Space Station and cementitious binding materials for lunar infrastructure. Here, we will investigate novel, low-cost nanomaterials that can be synthesized in high quantities to improve infrastructure in a variety of environments and withstand natural (flood, earthquake) and man-made (blast, impact, fire) threats. The REU student will focus on enhancing cement-based construction material properties. They will construct and test how sustainable cement-based composites are enhanced by adding a nano-additive, such as graphene. Specific material properties at the nanoscale will first be computationally assessed through utilizing numerical simulations to predict mechanical, physical, or thermal environments. Once the REU student has completed the computational model, they will be trained to conduct experiments, such as AFM imaging, nanoindentation, thermal analysis, and mechanical testing to analyze the efficacy of the computationally optimized cement-based composites. By the end of the project, the REU student will collect and summarize literature on nano-additives in cement, conduct numerical simulations, and validate the simulations experimentally.

D’Alessio Lab: The D’Alessio lab is focused on the fate and transport of pharmaceuticals and personal care products, sustainable water and wastewater treatments, and water reuse. The need for alternative sources of water is dramatically increasing due to demographic growth, economic development, the need to improve living standards, addressing climate change, and increased pollution. There is a challenge to feed the people by producing crops with less arable land and limited water resources. Where irrigation water is needed for crop production, wastewater (human and/or animal) treatment and reuse represents a viable alternative, leading to increased soil productivity. Depending on the wastewater source, the alternatives range from simple chemical disinfection to more complex systems integrating bioreactors, filtration membranes, and UV light, among others. Thus, there is a need for effective alternative wastewater treatments that are economically feasible and environmentally sound. Sand filtration (SF) is a technology that has been widely used due to its low costs and relative simplicity of construction and maintenance, but SF alone shows limited ability to remove micropollutants. A combination of SF with low-cost post-treatments (e.g., activated carbon with or without silver nanoparticles, graphinated sand, etc) or the use of sand coated with graphene, significantly improved contaminant removal.

Lopez Lab: Ion exchange membranes (IEMs) are widely used to produce organics, acids, bases, and more recently power generation through salient gradient energy. However, IEMs have a high propensity to foul when exposed to certain organics and suspended solids. Thus, development of improved IEMs with low fouling is needed to handle a larger variety of feed conditions for the specialty chemical industry. Functionalization of IEMs through nano-particulates presents an opportunity for improved antifouling performance as previous studies on nanofiltration membranes demonstrated a reduction in fouling and cake layer formation. The REU student will incorporate titanium oxide (TiO­₂) and carbon nanotubes (CNT) into IEMs and assess performance with electrodialysis separations and the antifouling capabilities possessed by modified membranes. The student will be trained by Dr. Lopez and a graduate student on the synthesis of functionalized IEMs through non-solvent phase inversion and spin coating methods. Membranes will be characterized via SEM, AFM, and FTIR-ATR under the guidance of the graduate student mentor. Electrodialysis performance will be assessed with clean and contaminated water solutions to determine the antifouling capabilities of functionalized membranes.

Prager Lab: Dr. Prager’s present research primarily involves the development of novel, cellulose-based materials for food packaging applications.  Her research group has completed several unique studies exploiting the supercritical impregnation of food-grade wax-based solutes into paper substrates, providing a substantial hydrophobic improvement into the sticky hydrophobic range (contact angle > 140^o).  Various exploration areas within this project have focused on optimizing the quantity of alkyl ketene dimer (AKD) impregnated into the paper; performing cloud-point solubility measurements of AKD and vegetable wax for future impregnation efforts; developing thermodynamic solubility models from this work; measuring the surface energy changes resulting from the impregnation; understanding the morphology of the resulting paper; and taking mechanical measurements to test the robustness of the material.  Her other main focus is on traditional paper coating methods using the nanoadditives cellulose nanocrystal (CNC) and cellulose nanofiber (CNF).  Both these additives have shown substantial improvement in the thermal barrier achieved upon coating the formulation onto paper.  Various optimization studies to assess the colloidal properties, and mechanical analyses, have also been performed with this work.  She is presently investigating the interfacial kinetics of AKD attaching onto cellulose biopolymers using a quartz crystal microbalance (QCM-D), and is discovering unique characteristics at the molecular level.

 

Computational Nanoengineering

Chen Lab: The Chen Lab develops novel statistical machine learning algorithms for nanoengineering and bioinformatics applications. Data embedding translates high-dimensional data to a relatively low-dimensional representation. It provides a principled way to visualize high-dimensional data and makes it easier to build machine learning models. For example, the Chen lab has used the approach of implementing multiple-instance learning in drug activity prediction. In this project, the REU student will explore different data embedding algorithms and apply them to benchmark data sets. The student will study four methods: principal component analysis (PCA), multidimensional scaling (MDS), self-organizing map (SOM), and t-distributed stochastic neighbor embedding (t-SNE). The student will learn the basics of Python through guidance and mentorship of the PI and graduate student, and use the Python scikit-learn package to apply these methods to benchmark data sets, such as those that map protein structure, bonding, and energetics. Throughout this project, the student will read literature on these and other relevant data embedding methods and be able to understand the theory behind each, ultimately gaining the skills necessary to make pointed design decisions when formulating the algorithms.

Li Lab: The Li lab is dedicated to unraveling sequence-structure-dynamics-function relationship of membrane proteins using cutting-edge computational chemistry and biology approaches. Our primary focus lies in investigating how missense mutations in ion channels can instigate protein dysfunction, ultimately contributing to the development of various diseases. The profound impact of disease-associated mutations in ion channels usually hinges on the dynamic structural transitions occurring within these proteins. To gain a comprehensive understanding of the pathophysiological consequences driven by these mutations, it is imperative to scrutinize the atomic-level alterations they induce in structural dynamics. The REU student will learn to employ a combination of bioinformatics and molecular dynamics (MD) simulations to probe the effects of specific mutations on the structural transitions within ion channels. Beginning with a literature meta-analysis and in-depth protein sequence analysis, the REU student will skillfully map the most up-to-date genetic data, pinpointing critical mutation hotspots. Subsequently, they will adeptly construct all-atom simulation systems for both the wild-type protein and its mutant counterparts using advanced molecular modeling techniques. Extensive MD simulations will be meticulously executed to shed light on how these mutations influence pivotal channel functions. Analyzing these MD trajectories will offer insights into the molecular mechanisms underlying mutation-driven phenotypes, thereby providing a foundation for designing drugs tailored to treat these diseases.

Nouranian Lab: The Engineering Materials Simulation Lab performs computations in nanoengineering, including the investigation of drug loading, release, and dynamics on different nanocarriers. We use molecular dynamics (MD) to probe phenomena at the nanoscale. One of our projects is to investigate the potential of N-trimethyl chitosan (TMC) as a Group A streptococci (GAS) vaccine delivery system. Roughly 95% of all GAS infections in the world are accounted for by 116 different M types. The N-terminal protective regions of the M proteins can be clustered into structurally and functionally related groups, and it is theoretically possible to protect against all prevalent M types using 30-35 M peptides in a multivalent vaccine. TMC nanoparticles have cationic surfaces that promote efficient cellular uptake. They also have other desirable properties, such as bio-availability, non-cytotoxicity, biodegradability, high aqueous solubility, muco-adhesion, and stability over a range of pH. In this project, MD simulations of select chitosan matrixed peptides will enable the prediction of peptide structures compared to structures in the Protein Data Base or simulated using PEP-FOLD or Rosetta de novo peptide structure prediction tools. Moreover, nanoparticle formation mechanisms, strengths of the M peptide-TMC interactions in an aqueous medium under physiological conditions, and possible TMC agglomeration will be explored. The REU student will undergo training in basic MD simulation, including activities related to pre-processing, production runs, and post-processing. The students will learn how to build the structures and perform sample runs. They will use these techniques to simulate M peptide proteins binding to TMC, M-peptide-TMC complex stability, and predict the ideal combination of M peptide epitopes for inclusion in a novel GAS nano-vaccine.

Wu Lab: The Wu Lab investigates 3D volume rendering of particulate matter and scalar plume in fluids. Transport of a discrete phase in fluids is ubiquitous in nature as well as in engineering applications. Particulate matter (e.g., PM 2.5 pollutant, pollen, ember) in the atmosphere, spilled oil droplets in water, respiratory aerosol exhausted by people, and fuel spray in the combustion chamber of engines are just a few examples. Current visualization and analysis tools for the discrete phase exhibit the scalar distribution, either mean, variation, or higher-order statistics like the probability density function, at iso-scalar values. 3D volume rendering is a technique that provides a full 3D view in which each point mimics a density proportional to the value of the field one wants to visualize, and 3D volume rendering software in python (K3D) can perform this analysis. The scalar field is rendered as randomly distributed dots in 3D with the concentration of dots proportional to the scalar to show the drops. The generate figure is rotatable and shows more details about the distribution. In this REU project, the UG student will integrate the K3D python code with existing particle/droplet dispersion data to visualize the distribution of nanoparticles by volume rendering. The available database includes Dr. Wu’s multiphase simulations of respiratory aerosol in atmospheric flow that was used to model the spread of COVID-19 through respiratory droplets. Other data sets of scalar transport in environmental flows, such as sand cloud formation during helicopter landing, are also available in the School of Engineering at UM. Upon completion of the project, the student is expected to be able to execute 3D volume rendering and design advanced visualization tools for engineering problems. The REU student will use these tools to determine how nanoscale contagion airborne transmission is affected by environmental variables, such as concentration, plume size, and ambient conditions.