Development and Application of New Tools to Study Cell and Tissue Physics
Faculty Mentor: Xin Tang
Project Description: Mechanical signals strongly influence embryological development, differentiation, morphogenesis, tissue patterning, and aging as well as various important biological functions. When mechanosensing, mechanotransduction, and mechanoresponse are misregulated, diseases usually occur or progress. For example, cancer deaths are mostly caused by metastasis of malignant cells that can be mechanically stimulated or selected. During metastasis, cancer cells detach from the primary tumor, spread to different body locations via the lymph system and/or blood circulatory system, reattach to invade the target organs and form the secondary malignant tumors. Interestingly, in contrast to healthy organs, primary tumors are often mechanically stiffer and tumor cells are often mechanically softer than their healthy counterparts. These altered mechanical signatures have been identified as one of the promoting signals to enhance metastasis. The innovation of biophysics and biochemistry technologies generally enables the dissection and manipulation of basic operating principles underlying these biological and pathological processes, leading to new potential therapeutics to improve health.
What the Participant Will Do: This multidisciplinary project contains experiment (60%), computation (20%), and theory (20%) components. No prior experience working on biological problems is required. All participants will be provided with training on live-cell imaging, design of novel biomaterials/optics, numerical simulation, and theory for mechanobiology and biophysics research. Students will apply these quantitative skills to investigate how biophysical forces influence the function and behavior of cancer and healthy cells.
2D Material Nano-Laminates for Selective Transport and/or Adsorption of Species
Faculty Mentor: Saeed Moghaddam
Project Description: The objective of this research is to determine the effect of different synthesis conditions on transport characteristics of a bilayer Graphene Oxide (GO) structure as the active layer of a Nano-Filtration (NF) membrane. The proposed structure is an order of magnitude thinner than the active layer of existing NF membranes (100-200 nm). Preliminary results on a membrane (prepared without optimizations) show 3-4 times less energy consumption compared to the state-of-the-art NF and Reverse Osmosis (RO) membranes. This new membrane can be a viable solution for low-cost removal of Endocrine Disrupting Chemicals (EDCs) from water resources, as recent scientific reports have provided evidence of adverse reproductive outcomes (infertility, cancers, and malformations) from exposure to EDCs. Although the existing NF and RO membranes have been shown to separate organic micropollutants effectively, they suffer from high energy use. To realize the potential of GO-based NF membranes in energy-efficient cleaning of drinking water, it is essential to develop a comprehensive understanding of the effect of physicochemical properties of the GO nanoplatelets and their interlinking molecules on transport characteristics of the GO bilayer. The effects of oxidation process, nanoplatelets size, defects size and density, and the interlinking molecule on water permeation and EDCs rejection rates will be studied.The student will be trained on the science of species transport through nanostructures and testing methods.
Solar Thermochemical Water Splitting to Produce H2 Fuel
Faculty Mentor: Jonathan Scheffe
Project Description: Conversion of solar energy to chemical fuels, such as molecular hydrogen (H2) or synthesis gas (syngas), via a thermochemical process provides a potential pathway towards clean renewable energy that can be stored for long periods of time and transported over large distances. The metal-oxide (shown generically below as MxOy) based thermochemical redox cycle is one such method of solar fuel production. A typical metal-oxide based redox cycle is characterized by two reactions occurring in separate steps. The first step, driven by solar energy, involves endothermic reduction of the metal-oxide, resulting in the evolution of oxygen from the crystal structure of the metal-oxide. In the exothermic second step, the reduced metal-oxide is oxidized with steam (H2O) to produce H2 or with a mixture of H2O and carbon dioxide (CO2) to produce syngas.
What the Participant Will Do: The main purpose of this research project to experimentally evaluate and compare the performance of candidate metal oxide materials that are hypothesized to produce greater H2 yields compared to the state of the art oxide, nonstoichiometric ceria. This is part of a larger Department of Energy sponsored project entitled “A New Paradigm for Materials Discovery and Development for Lower Temperature and Isothermal Thermochemical H2 Production” and will involve collaboration with computational and materials synthesis experts in Materials Science and Engineering at UF.
Interaction between Needle Surfaces and Tissues during Biopsy
Faculty Mentor: Hitomi Greenslet
Project Description: Needle biopsy procedures are used to extract tissue samples for cancer diagnosis. It has been hypothesized that the combination of lower needle insertion force, including friction between the tissue and needle surface, and less needle deflection leads to a more effective biopsy procedure, such as one that more accurately extracts a larger amount of tissue from a lesion with less damage. Based on this hypothesis, a new coaxial needle system was created to enable the extraction of more tissue with less damage. The preliminary study found that the clearance between the inner stylette and outer needle and the needle insertion speed are the key factors affecting the needle insertion force and amount of tissue extracted. This project aims to clarify the mechanism behind that trend by analyzing the interaction between the needle surface and tissue during a biopsy.
What the Participant Will Do: The student will run biopsy tests using chicken breast and phantom tissue (e.g., gelatin and polymers) and collect data (including needle-insertion force, in situ tissue movement during biopsy, and extracted tissue weight, geometry and condition). The student will learn how to design experiments, collect and analyze data, and summarize the findings. The student will clarify the relationships between the movement of tissue on the needle surface, friction between the tissue and needle surface, and amount and condition of the extracted tissue, which will result in the discovery of fundamental knowledge related to the tissue–needle interaction and tissue-damaging mechanisms during biopsy.
Control of Inflammation-Mediated Coagulopathy
Faculty Mentor: Amor Menezes
Project Description: This project investigates the use of feedback control to manipulate the concentrations of proteins that are involved in inflammation-mediated coagulation disorders. Two disorders that we focus on are: (1) trauma-induced coagulopathy, which has an incidence of 25% among severely injured patients, is characterized by uncontrolled bleeding, and has an associated 35-50% mortality; and (2) infection (COVID-19)-induced coagulopathy in the lung, which results in blood clots (composed of fibrin). We employ feedback control and dynamical systems theory so as to intervene at any timepoint, or even at multiple timepoints, in a patient’s pathophysiological trajectory. Moreover, we are able to modulate protein concentrations in a patient-tailored way, thereby realizing personalized and precision medicine. Our long-term vision is to develop a platform technology that consists of engineered cellular control circuits capable of directly sensing and treating diseased cells, tissues, and organs.
What the Participant Will Do: This project will involve both wet lab (70%) and dry lab (30%) components. The REU participant will be provided with training on: instruments that interrogate clotting in blood samples; manipulating protein concentrations; culturing alveolar epithelial cells; imaging cells; modeling regulatory networks like the coagulation cascade; and designing biological control systems. The student will then apply these skills to computationally predict and experimentally mitigate a coagulopathic phenotype.
Control Development and Testing using Functional Electrical Stimulation
Faculty Mentor: Warren Dixon
Project Description: Functional electrical stimulation (FES) is a rehabilitation technique in which an electric current is applied across a muscle group to activate motor neurons and induce muscle contractions to perform a functional task such as cycling. Motorized FES induced cycling is a common rehabilitative treatment since it involves repetitive low impact coordination of the limbs. By switching the stimulation across different muscle groups so that each muscle contributes only to the forward motion of the cycle’s crank angle, a nonlinear state-dependent switched system arises. Since there are unstable regions of the crank cycle in which the legs are inefficient at producing torque, the control strategy can intermittently switch between different muscle groups and a motor to help reduce fatigue, allowing for more repetitions.
What the Participant Will Do: During the first week, the participant will be introduced to the Institutional Review Board (IRB) process and the protocol and procedures for performing control experiments on people. The following weeks they will learn how to interface the computer and software with the electrical stimulator and electrodes, and observe experimental procedures being performed. Participants will be given tutorial information about the basic switching control structure and will be provided software that encodes such algorithms. Participants will then perform experiments on volunteers using the buddy system while adhering to safety policies and practices. They will also perform statistical analysis tests to determine cause effect relationships and correlations in the experimental data.
Atomistic Modeling of the Dynamic Fracture in Hydrogels
Faculty Mentor: Douglas Spearot
Project Description: Hydrogels are comprised of a mechanically or chemically cross-linked hydrophilic polymer network immersed in a matrix of absorbed water molecules. Hydrogels are biocompatible and have been used extensively in advanced biomedical applications such as in tissue scaffolds, in vivo studies of traumatic brain injury, and repair or replacement of damaged tissue. The objective of this project is to investigate crack propagation in hydrogels during dynamic loading conditions using classical atomistic simulations. Specifically, computational methods will be employed to construct hydrogel models with different water contents, molecular weights or defect contents. Molecular dynamics simulations will then be employed to study crack propagation during dynamic loading conditions.
What the Participant Will Do: This project is computationally focused. The participant will be provided access to the University of Florida high-performance computing system (HiPerGator) and will learn how to conduct atomistic simulations of hydrogel behavior. The student will use an existing simulation code — no programming experience is required although familiarity with Matlab or Python for data analysis is recommended.
Development of Hand-Held Devices for Pathogen Detection
Faculty Mentor: Z. Hugh Fan
Project Description: Viruses are a global public health problem, evidenced from the pandemic of coronavirus disease 2019 (COVID-19). It is highly desirable to have a device that can detect viruses for transmission control and differentiate various viruses for disease-specific clinical care. To meet the need, the objective of this project is to develop a rapid and cost-effective platform for detecting pathogens at the point of care. The platform will disintegrate pathogens (a process called lysis) and perform isothermal amplification of enriched nucleic acids, followed by colorimetric detection by naked eye or a smartphone camera. Innovation is needed in the device miniaturization, sequential reagent delivery, and operation in the field without power and laboratory equipment. The project is a part of the lab’s efforts on microfluidics, which is an interdisciplinary field involving engineering, sciences, and medicine.
What the Participant Will Do: This project is experimentally focused. The student will be trained to fabricate devices, including 3D printing, lamination, and integration. The devices will then be tested by the student while being trained on valving control, assays, and detection. Various detection schemes and conditions will be investigated, and their effects on detection sensitivities will be studied. The student is encouraged to test their own ideas after training and understanding the challenges associated with the project.
New Classes of Fluid Instabilities in 3D Printing of Soft Matter
Faculty Mentor: Thomas E. Angelini
Project Description: Technology for 3D printing with hard materials is in a very mature state; hobbyists can 3D print hard thermoplastics with high precision at low costs. Many important applications in healthcare require the use of soft materials, like hydrogels and elastomers, which have the feel of Jell-O or soft rubber. The recent invention of a soft matter 3D printing technique at UF has opened the door to 3D printing precise objects made from soft matter. However, the new combinations of complex soft materials involved in this 3D printing technique have generated unanticipated fluid instabilities. The physical principles that control these instabilities have not yet been determined, limiting the ability to advance the technology.
What the Participant Will Do: The REU student will 3D print a diversity of different shapes like lines, spheres, cylinders, and planes and study their evolution under destabilizing forces. The shapes will be made from a viscous or viscoelastic liquid and suspended in 3D space without any support apart from an embedding continuum. The embedding material is a granular-gel based liquid-like solid, which is a solid from a thermodynamic perspective yet also possesses many of the properties of a liquid. The student will perform time-lapse microscopy and photography and learn digital image processing techniques for data analysis.
Mechanobiology of Wound Healing
Faculty Mentor: Chelsey Simmons
Project Description: While many amphibians can regrow entire limbs and organs, examples of mammalian regeneration are very limited. Recently, the Simmons group has identified a remarkable mammal that has regenerative ability: The African Spiny Mouse (Acomys). Preliminary data from collaborations between the Simmons group and medical and biology researchers across UF are exciting and intriguing: Acomys tissues do not exhibit fibrosis (scarring) when repairing damage. Understanding fibrosis is thus the key to unlocking the secrets of regeneration. With the Acomys model and an innovative suite of tunable mechanical microenvironments, this research enables a complete system to identify the role of mechanical strain on scar-free wound healing.
What the Participant Will Do: The REU Participant will perform research to test the hypothesis that mechanical stimuli can direct regeneration by providing controlled mechanical stimulation of cells from regenerative (Acomys) and normal (Mus) mice. During the first two weeks of the program, the student will learn how to fabricate hydrogels and run wound healing assays, along with receiving pertinent hands-on safety training.