100th Anniversary of Macromolecular Science Viewpoint: Opportunities in the Physics of Sequence-Defined Polymers

Polymer science has been driven by ever-increasing molecular complexity, as polymer synthesis expands an already-vast palette of chemical and architectural parameter space. Copolymers represent a key example, where simple homopolymers have given rise to random, alternating, gradient, and block copolymers. Polymer physics has provided the insight needed to explore this monomer sequence parameter space. The future of polymer science, however, must contend with further increases in monomer precision, as this class of macromolecules moves ever closer to the sequence-monodisperse polymers that are the workhorses of biology. The advent of sequence-defined polymers gives rise to opportunities for material design, with increasing levels of chemical information being incorporated into long-chain molecules; however, this also raises questions that polymer physics must address. What properties uniquely emerge from sequence-definition? Is this circumstance-dependent? How do we define and think about sequence dispersity? How do we think about a hierarchy of sequence effects? Are more sophisticated characterization methods, as well as theoretical and computational tools, needed to understand this class of macromolecules? The answers to these questions touch on many difficult scientific challenges, setting the stage for a rich future for sequence-defined polymers in polymer physics

Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

There are many areas in medicine and industry where it would be advantageous to orally deliver bioactive proteins and peptides (BPPs), including ACE inhibitors, antimicrobials, antioxidants, hormones, enzymes, and vaccines. A major challenge in this area is that many BPPs degrade during storage of the product or during passage through the human gut, thereby losing their activity. Moreover, many BPPs have undesirable taste profiles (such as bitterness or astringency), which makes them unpleasant to consume. These challenges can often be overcome by encapsulating them within colloidal particles that protect them from any adverse conditions in their environment, but then release them at the desired site-of-action, which may be inside the gut or body. This article begins with a discussion of BPP characteristics and the hurdles involved in their delivery. It then highlights the characteristics of colloidal particles that can be manipulated to create effective BPP-delivery systems, including particle composition, size, and interfacial properties. The factors impacting the functional performance of colloidal delivery systems are then highlighted, including their loading capacity, encapsulation efficiency, protective properties, retention/release properties, and stability. Different kinds of colloidal delivery systems suitable for encapsulation of BPPs are then reviewed, such as microemulsions, emulsions, solid lipid particles, liposomes, and microgels. Finally, some examples of the use of colloidal delivery systems for delivery of specific BPPs are given, including hormones, enzymes, vaccines, antimicrobials, and ACE inhibitors. An emphasis is on the development of food-grade colloidal delivery systems, which could be used in functional or medical food applications. The knowledge presented should facilitate the design of more effective vehicles for the oral delivery of bioactive proteins and peptides

Recent progress in the science of complex coacervation

Complex coacervation is an associative, liquid–liquid phase separation that can occur in solutions of oppositely-charged macromolecular species, such as proteins, polymers, and colloids. This process results in a coacervate phase, which is a dense mix of the oppositely-charged components, and a supernatant phase, which is primarily devoid of these same species. First observed almost a century ago, coacervates have since found relevance in a wide range of applications; they are used in personal care and food products, cutting edge biotechnology, and as a motif for materials design and self-assembly. There has recently been a renaissance in our understanding of this important class of material phenomena, bringing the science of coacervation to the forefront of polymer and colloid science, biophysics, and industrial materials design. In this review, we describe the emergence of a number of these new research directions, specifically in the context of polymer–polymer complex coacervates, which are inspired by a number of key physical and chemical insights and driven by a diverse range of experimental, theoretical, and computational approaches

Phase Separation: Bridging Polymer Physics and Biology

Significant parallels exist between the phase separation behavior of polymers in solution and the types of biomolecular condensates, or ‘membraneless organelles,’ that are of increasing interest in living systems. Liquid-liquid phase separation allows for compartmentalization and the sequestration of materials, and can be harnessed as a sensitive strategy for responding to small changes in the environment. Here, I review many of the parallels and synergies between ongoing efforts to study and take advantage of phase separation in living vs. synthetic materials

The Effect of GnRH at Time of Insemination on Initiation of LH Pulses and Subsequent Progesterone

Research has indicated that luteinizing hormone (LH) pulses play a vital role in corpus luteum (CL) formation and subsequent progesterone concentrations. Therefore, our objectives were to determine: 1) when LH pulses begin following onset of estrus, 2) the effect an injection of gonadotropin releasing hormone (GnRH) would have on initiation of LH pulses, and 3) the effect LH pulse initiation had on subsequent plasma progesterone concentrations. Cows were synchronized with the Select Synch + Controlled Internal Drug Releasing device (CIDR) protocol (d -7 100 μg GnRH and CIDR; d 0 25 mg prostaglandin (PG) and removal of CIDR; estrus detected with HeatWatch). Following detection in estrus, a jugular catheter was inserted in each cow (n = 10). Based on initiation of estrus, cows were allotted into two treatments: 1) GnRH given 12 h (12.5 ± 1.2 h) after the initiation of estrus (n = 5; 100 μg) and 2) Control (n = 5). Blood samples were collected at 15-min intervals for 6 h at 12 h (bleed 1), 26 h (bleed 2), 40 h (bleed 3), 54 h (bleed 4), and 68 h (bleed 5) after the onset of estrus. The interval from onset of estrus to bleed 1 and ovulation was similar between treatments. The GnRH cows tended to have a greater area under the LH curve for bleed 1 compared to control cows. No differences were detected in bleeds 2, 3, 4, or 5. Average concentration of LH for GnRH cows in bleed 1 tended to be greater than control. No differences were detected in bleeds 2, 3, 4, or 5. No differences were detected in pulse frequency between treatments in bleeds 1, 3, 4, or 5, but in bleed 2, control tended to have more pulses than GnRH (2.5 ± 0.5 vs 1.4 ± 0.4). The GnRH-treated cows tended to have greater subsequent progesterone concentrations; however, GnRH-treated cows that had no LH pulses during bleed 2 had lower progesterone concentrations than cows with pulses (control or GnRH). In summary, injecting cows with GnRH approximately 12 h after the onset of estrus tended to reduce LH pulses 26-32 h following initiation of estrus, and elimination of LH pulses between 26-32 h resulted in decreased concentrations of progesterone during the subsequent cycle

Design Rules for Encapsulating Proteins into Complex Coacervates

We investigated the encapsulation of the model proteins bovine serum albumin (BSA), human hemoglobin (Hb), and hen egg white lysozyme (HEWL) into two-polymer complex coacervates as a function of polymer and solution conditions. Electrostatic parameters such as pH, protein net charge, salt concentration, and polymer charge density can be used to modulate protein uptake. While the use of a two-polymer coacervation system enables the encapsulation of weakly charged proteins that would otherwise require chemical modification to facilitate electrostatic complexation, we observed significantly higher uptake for proteins whose structure includes a cluster of like-charged residues on the protein surface. In addition to enhancing uptake, the presence of a charge patch also increased the sensitivity of the system to modulation by other parameters, including the length of the complexing polymers. Lastly, our results suggest that the distribution of charge on a protein surface may lead to different scaling behaviour for both the encapsulation efficiency and partition coefficient as a function of the absolute difference between the protein isoelectric point and the solution pH. These results provide insight into possible biophysical mechanisms whereby cells can control the uptake of proteins into coacervate-like granules, and suggest future utility in applications ranging from medicine and sensing to remediation and biocatalysis

Obituary for Prof. Paul Dubin

On May 23rd, 2018, Paul Dubin, Research Professor of Chemistry at the University of Massachusetts Amherst, passed away at the age of 77. Dubin was born in 1941 in New York City to Carolyn and George Dubin. He graduated from the Bronx High School of Science, City College of New York, in 1962, and received his PhD at Rutgers University in New Jersey in 1970 under the supervision of Ulrich P. Strauss. He went on to postdoctoral studies with Frank E. Karasz at the University of Massachusetts Amherst and David A. Brant at the University of California, Irvine from 1970–1972. Dubin worked as a research scientist at Dynapol, Memorex Corp., and Clairol Research Laboratories before joining the faculty in the Department of Chemistry at Indiana University–Purdue University Indianapolis, where he remained for most of his professional life. In 2005 Dubin returned to the University of Massachusetts Amherst as a part-time Research Professor

PRISM-Based Theory of Complex Coacervation: Excluded Volume versus Chain Correlation

Aqueous solutions of oppositely charged polyelectrolytes can undergo liquid–liquid phase separation into materials known as complex coacervates. These coacervates have been a subject of intense experimental and theoretical interest. Efforts to provide a physical description of complex coacervates have led to a number of theories that qualitatively (and sometimes quantitatively) agree with experimental data. However, this agreement often occurs in a degeneracy of models with profoundly different starting assumptions and different levels of sophistication. Theoretical difficulties in these systems are similar to those in most polyelectrolyte systems where charged species are highly correlated. These highly correlated systems can be described using liquid state (LS) integral equation theories, which surpass mean-field theories by providing information on local charge ordering. We extend these ideas to complex coacervate systems using PRISM-type theories and are able to capture effects not observable in traditional coacervate models, particularly connectivity and excluded volume effects. We can thus bridge two traditional but incommensurate theories meant to describe complex coacervates: the Voorn–Overbeek theory and counterion release. Importantly, we hypothesize that a cancellation of connectivity and excluded volume effects provides an explanation for the ability of Voorn–Overbeek theory to fit experimental data despite its well-known approximations

A Student-Created, Open Access, Living Textbook

Textbooks are expensive, updated infrequently, and rarely used effectively by students. We discuss here a way for students to create the textbook for the course, helping them feel ownership over the course material. This Wiki-based, student-created textbook is online free for use, widely accessible by all, and editable during the course of and as topics evolve. This type of textbook format is particularly well suited to upper-level electives on topics that are rapidly emerging. We have nucleated a student created textbook here, fully online and open access, for two upper elective courses in chemical engineering. Wikis offer an easy-to-learn platform that does not require previous training in coding, and we have found it to be an excellent way to increase student learning while encouraging student buy-in and ownership of their course textbook