(7bp) Advanced Biologic-Synthetic Composites

Synergistic combinations of synthetic and natural components have yielded advanced biological, thermal, and mechanical properties and intricate hierarchical assemblies that have enabled impactful technologies in medicine, engineering, and environmental remediation. Yet, there remains extensive untapped knowledge of the ways in which synthetic materials interact with living systems, and of the ways in which to harness Nature’s functional, dynamic, and adaptable materials systems within the versatile, tunable frameworks of synthetic polymeric materials. Building on my graduate and postdoctoral research experiences on the synthesis, characterization, and assembly of functional polymers incorporating biological and biomimetic components, my independent research program will aim to engineer adaptive, modular composites from synthetic polymers and oligopeptides. I am interested in leveraging various polymer and peptide interactions to construct materials that disintegrate, form, or reform on-demand to capture or release active substances or to adjust mechanical properties in response to environmental cues. To this end, specific interactions between opposite-handed helical oligopeptides will be investigated as dynamic junctions within nanostructures, colloids, and hydrogels. Additionally, competition and cooperation between various interactions programmed into a given construct will be explored as a means to structure or re-structure materials in response to various inputs. For example, thermally-induced mesogen packing will be examined as a way to promote or suppress fibrillation of peptides tethered to the same scaffold. Further, I am interested to determine the role liquid-liquid and biological interfaces in the construction and assembly of biologic-synthetic composites. Interfacial mediation, acceleration, and patterning of polymer and peptide interactions is envisioned to yield complex hierarchical structures and streamline fabrication processes. Continual development and optimization of accessible, scalable methods for materials preparation represents an important goal of my proposed research program, as it will position these materials well for scale-up and translation to clinical and industrial implementation.

Research experience:

Ph.D. Dissertation Research: Functional hydrophilic polymers for solution assembly and non-viral gene therapy

Polymer Science & Engineering Department, University of Massachusetts Amherst, Thesis Advisors: Todd Emrick and Ryan C. Hayward

My graduate research involved the synthesis and assembly of functional hydrophilic polymers designed in linear and comb architectures to generate responsive emulsion-based materials and high-performance non-viral gene therapy reagents. Cationic oligopeptides facilitated complexation of nucleic acids and interaction with cellular and nuclear membranes, while zwitterionic groups imparted stimuli-responsive solution properties, reversible adhesion between emulsion droplets, and tunable polymer-nucleic acid binding strength. Reactive units enabled interfacial reactions on emulsion droplets that afforded robust capsules and triggered transitions from adhesive droplet gels to fluidic emulsions. Polymer architecture significantly impacted the performance of the cationic gene therapy reagents; comb polymers exhibited weaker polymer-nucleic acid binding strengths and afforded higher levels of gene expression compared to analogous linear systems. The high functionality of oligopeptide sequences within these polymer constructs inspired the direction of my independent research program, which will benefit from technical expertise gained during these studies.

Postdoctoral Research: Exploring impacts of stereochemistry on assembly of amphiphilic block copolypeptides

Department of Chemistry, Texas A&M University, Advisor: Karen L. Wooley

We are investigating the impact of stereochemical configuration of amphiphilic block polypeptides on solution-state and interface-mediated assembly to contribute fundamental understanding on stereochemistry-directed assembly and to address challenges in the treatment of recurrent urinary tract infections. To improve internalization of antimicrobial-loaded nanostructures into bladder cells, anisotropic particles > 100 nm in length presenting mannose-binding groups are desired to span multiple binding sites spaced approximately 20 nm apart on cell surfaces. Given that complexation of complementary stereoregular polymers (e.g., syndiotactic and isotactic poly(methyl methacrylate), poly(l-lactic acid) and poly(d-lactic acid), etc.) impacts solubility and stabilizes micelles with stereoregular hydrophobic cores, we anticipated that programming the stereochemistry of individual blocks of amphiphilic block polypeptides would allow access to non-spherical morphologies. Further, dramatic changes in thermal and mechanical properties reported upon complexation of stereoregular polymers suggests the potential for imparting advantageous materials properties, such as controlled release of antimicrobials. Well-defined block polypeptides, in which the stereochemistry of each block was dictated by that of the corresponding monomer, were synthesized and assembled into spherical and cylindrical nanostructures. Preliminary solid- and solution-state atomic force microscopy revealed distinct differences in the dispersion of polypeptide nanostructures with left- vs. right-handed helical hydrophilic shells connected to left-handed helical hydrophobic cores. Motivated by the power of stereocomplexation in bulk polymers and nanoscale assemblies, I wish to further pursue these interactions in my independent research program towards reformable materials with dynamic junctions composed of stereocomplexed oligopeptides. In this context, the rich functional and compositional variety of natural and non-canonical amino acids offers an exciting feedstock from which to pioneer the development of tailorable, adaptive materials systems poised to meet central challenges in medicine and engineering.

Teaching Interests:

Through classes, my research group, and outreach and service activities, I aspire to guide students and mentees toward fundamental scientific and engineering principles, quality, safe, and ethical scientific practices, and proficiency in oral and written communication. Future technological advances rely on the continual mentorship of the next generation of scientists and engineers, and having worked with outstanding mentors, I recognize the importance of endowing young scientists with technical, leadership, and communication skills within an empowering, collaborative, and interdisciplinary environment. Therefore, my classes will integrate recent discoveries in fundamental and applied research at universities, national laboratories, and companies to inspire students toward creative problem-solving in a variety of contexts. Quality, safe, and ethical practices will be discussed as they relate to concepts taught in the classroom, encountered in the laboratory and in research meetings, and reported in the literature and general media. Collaborative work has been an essential component of my graduate and postdoctoral research experience, and will be encouraged through classroom-based group problem-solving activities, as well as in my research program through intra- and inter-group collaborative research to promote innovation and develop communication skills. Written assignments and oral presentations in the classroom, preparation of manuscripts and research presentations, and involvement of my research group in the proposal drafting process will assist in developing essential communication skills. Finally, I am committed to being an active leader in service, outreach, and in the promotion of diversity, and wish to both participate in and lead activities that encourage engagement in science and engineering by future scientists and engineers, and the general public. I will recruit volunteers from my classes, research group, and department as further opportunities to improve communication skills and to enkindle interest in pursuing education, service, and outreach in their own careers.

Given my research and education background spanning chemical engineering, chemistry, and polymer-based materials science disciplines, I very much look forward to drawing from my polymer background to apply elements of polymer science to teaching chemical engineering core classes. Among the chemical engineering core classes, I am most interested in teaching introductory chemical engineering, thermodynamics, reaction kinetics, separations, and transport phenomena. Non-Newtonian flow behaviors exhibited by polymers, as well as processing techniques, such as spin-coating, electrospinning, and extrusion, will provide stimulating, industrially-relevant examples with which to explore fluid dynamics. Similarly, size exclusion chromatography used routinely in industrial and research environments to characterize polymer molecular weight can be included in separations classes, while polymer purification by dialysis represents a tangible example with which to teach equilibration across a semi-permeable membrane. Apart from core classes, I am keen to design a course on scientific written and oral communication and interdisciplinary courses related to polymer synthesis and characterization.

Selected service, leadership, and outreach activities:

Vice President, Postdoctoral Association of Chemistry, February 2017-present: Co-organized networking and professional development events for postdoctoral associates

Science Night, Lead organizer, April 2017: Coordinated the organization of a science night at a local elementary school, in which approximately 300 students engaged in 13 activities contributed by S.T.E.M. groups at Texas A&M University and two local companies

NSF East Asia Pacific Summer Institutes (EAPSI) Singapore Alumni Resource Advisor, 2015 and 2017: Prepared a presentation and documents to assist new fellows in making the most of their international research experience

University of Massachusetts Amherst Polymer Science & Engineering ASPIRE (A Student-led Program in Research and Education) program, 2013-2015: Designed a polymer hydrogel module implemented in the 2014 and 2015 programs

Selected Publications (10 total, 4 first author, 22 citations):

Letteri RA*, Santa Chalarca CF*, Bai Y, Hayward RC, Emrick T. “Forming sticky droplets from slippery polymer zwitterions.” Advanced Materials, in press. *Equal contributors

Zigmond, JS, Letteri RA, Wooley KL. “Amphiphilic Cross-Linked Liquid Crystalline Fluoropolymer-Poly(ethylene glycol) Coatings for Application in Challenging Conditions: Comparative study between Different Liquid Crystalline Comonomers and Polymer Architectures.” ACS Appl. Mater. Interfaces 2016, 8, 33386-33393

Ghobadi AF*, Letteri R*, Parelkar SS, Zhao Y, Chan-Seng D, Emrick T, Jayaraman A. “Dispersing Zwitterions into Comb Polymers for Nonviral Transfection: Experiments and Molecular Simulation.” Biomacromolecules 2016, 17, 546-557. *Equal contributors

Chang CC*, Letteri R*, Hayward RC, Emrick T. “Functional Sulfobetaine Polymers: Synthesis and Salt-Responsive Stabilization of Oil-in-Water Droplets.” Macromolecules 2015, 48, 7843-7850. *Equal contributors

Parelkar S*, Letteri R*, Chan-Seng D*, Zolochevska O, Ellis J, Figueiredo M, Emrick T. “Effect of oligopeptide orientation on polymer-based DNA delivery.” Biomacromolecules 2014, 15, 1328-1336. *Equal contributors