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1. The Complexation Properties of Self-Defensive Microgel-Modified Antimicrobial Surfaces

   https://doi.org/10.1021/acsabm.5c02096  

   Guo, Yunhua; Yin, Zhuozhuo; Wang, Hongjun; Paren, Benjamin; Wasik, Patryk; Wadurkar, Anand; Ji, Jingjing; Nangia, Shikha; Gill, Nicole; Sauer, Karin; et al (February 2026, ACS Applied Bio Materials)

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   The complexation of cationic antimicrobials with polyanionic microgels on a biomaterial surface can render that surface self-defensive against bacteria by killing those bacteria which physically contact the antimicrobial-loaded microgels. This killing has been attributed to the contact-driven transfer of antimicrobial from a microgel to a challenging bacterium, though much remains unknown about this process. Here we use a combination of experiments and computational modeling to identify key aspects of the complexation phenomena which influence the self-defensive properties. We synthesize poly(acrylic acid) (PAA) microgels (∼2-5 μm diameter) via membrane emulsification and electrostatically deposit them onto polycaprolactone (PCL) coupons or onto glass to form a discontinuous submonolayer. Subsequent microgel loading with colistin or with Sub5 antimicrobial peptide (AMP) causes microgel deswelling. Under physiological conditions Sub5 remains stably sequestered whereas colistin is quickly released. Coarse-grained molecular dynamics (CGMD) simulations confirm stronger Sub5/PAA complexation. CGMD calculations also indicate that Sub5 forms dimers and higher-order structures, a prediction confirmed experimentally by Small-Angle X-ray Scattering (SAXS). Supramolecular structure entropically enhances the complexation strength because of enhanced counterion release per complexation event, and this finding can help identify other antimicrobials well suited for such a nonelutive yet self-defensive strategy. CGMD simulations also show that Sub5 has a higher complexation strength with the Staphylococcus aureus membrane than it does with PAA, confirming that there is a thermodynamic driving force for antimicrobial transfer. Such self-defensive surfaces significantly reduce S. aureus colonization (over 90% reduction relative to unmodified controls) in an in vitro hematogenous contamination model and remain cyto-compatible as evidenced by mesenchymal stem cell spreading and proliferation 

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2. Osmotic swelling behavior of surface-charged ionic microgels

   https://doi.org/10.1063/5.0161027  

   Alziyadi, Mohammed O; Denton, Alan R (November 2023, The Journal of Chemical Physics)

   In recent years, ionic microgels have garnered much attention due to their unique properties, especially their stimulus-sensitive swelling behavior. The tunable response of these soft, permeable, compressible, charged colloidal particles is increasingly attractive for applications in medicine and biotechnologies, such as controlled drug delivery, tissue engineering, and biosensing. The ability to model and predict variation of the osmotic pressure of a single microgel with respect to changes in particle properties and environmental conditions proves vital to such applications. In this work, we apply both nonlinear Poisson–Boltzmann theory and molecular dynamics simulation to ionic microgels (macroions) in the cell model to compute density profiles of microions (counterions, coions), single-microgel osmotic pressure, and equilibrium swelling ratios of spherical microgels whose fixed charge is confined to the macroion surface. The basis of our approach is an exact theorem that relates the electrostatic component of the osmotic pressure to the microion density profiles. Close agreement between theory and simulation serves as a consistency check to validate our approach. We predict that surface-charged microgels progressively deswell with increasing microgel concentration, starting well below close packing, and with increasing salt concentration, in qualitative agreement with experiments. Comparison with previous results for microgels with fixed charge uniformly distributed over their volume demonstrates that surface-charged microgels deswell more rapidly than volume-charged microgels. We conclude that swelling behavior of ionic microgels in solution is sensitive to the distribution of fixed charge within the polymer-network gel and strongly depends on bulk concentrations of both microgels and salt ions. 

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3. Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation

   https://doi.org/10.3390/polym11091406  

   Levit, Shani L.; Walker, Rebecca C.; Tang, Christina (September 2019, Polymers)

   Flash NanoPrecipitation (FNP) is a rapid method for encapsulating hydrophobic materials in polymer nanoparticles with high loading capacity. Encapsulating biologics such as proteins remains a challenge due to their low hydrophobicity (logP < 6) and current methods require multiple processing steps. In this work, we report rapid, single-step protein encapsulation via FNP using bovine serum albumin (BSA) as a model protein. Nanoparticle formation involves complexation and precipitation of protein with tannic acid and stabilization with a cationic polyelectrolyte. Nanoparticle self-assembly is driven by hydrogen bonding and electrostatic interactions. Using this approach, high encapsulation efficiency (up to ~80%) of protein can be achieved. The resulting nanoparticles are stable at physiological pH and ionic strength. Overall, FNP is a rapid, efficient platform for encapsulating proteins for various applications. 

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4. STUDYING THE EFFECT OF CROSSLINKER ON POLYMERIC MICROGELS

   https://doi.org/10.18061/ojs.v118i1  

   Tietjen, C. Samantha; Hudson, Samantha; Streletzky, Kiril A. (January 2018, The Ohio journal of science)

   Microgels are spherical particles suspended in solution, comprised of crosslinked polymer chains. Due to the amphiphilic property of the parent polymer, microgels display a temperature dependent volume phase transition (de-swelling), and thus have the potential to be used for drug delivery. Previous studies suggest that increasing the concentrations of the chemical cross-linker reduces the hydrodynamic radius (Rh) and the de-swelling ability, thus primary experiments focused on the variation of cross-linker to polymer ratios. Microgels were synthesized using the polysaccharide polymer hydroxypropyl cellulose (HPC) and chemical cross-linker divinyl sulfone (DVS), in a surfactant solution. Synthesized particles were characterized using dynamic light scattering (DLS) for temperature and angular dependence to study their shape and determine the apparent Rh of the swollen and de-swollen states. Initial microgel synthesis revealed a dependence of Rh on microgel concentration in samples, requiring a correction for infinite sample dilution during analysis. Increasing DVS:HPC ratio from 1 to 30 causes Rh to decrease from 150 to 190 nm at 25 °C, and from 65 to 95 nm at 50 °C. Ratios from 40 to 50 resulted in swelling from 70 nm at 25 °C to 165 nm at 50 °C. At a ratio of 60, an apparent bulk gelation occurred. The increase in DVS:HPC ratio allowed for the controlled synthesis of more compact microgels that display reversible temperature controlled deswelling. However, at ratios above 30, particles were found to grow in size above the transition temperature. 

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5. Cognate DNA Recognition by Engrailed Homeodomain Involves a Conformational Change Controlled via an Electrostatic-Spring-Loaded Latch

   https://doi.org/10.3390/ijms23052412  

   D’Amelio, Nicola; Tanielian, Benjamin; Sadqi, Mourad; López-Navajas, Pilar; Muñoz, Victor (March 2022, International Journal of Molecular Sciences)

   Transcription factors must scan genomic DNA, recognize the cognate sequence of their control element(s), and bind tightly to them. The DNA recognition process is primarily carried out by their DNA binding domains (DBD), which interact with the cognate site with high affinity and more weakly with any other DNA sequence. DBDs are generally thought to bind to their cognate DNA without changing conformation (lock-and-key). Here, we used nuclear magnetic resonance and circular dichroism to investigate the interplay between DNA recognition and DBD conformation in the engrailed homeodomain (enHD), as a model case for the homeodomain family of eukaryotic DBDs. We found that the conformational ensemble of enHD is rather flexible and becomes gradually more disordered as ionic strength decreases following a Debye–Hückel’s dependence. Our analysis indicates that enHD’s response to ionic strength is mediated by a built-in electrostatic spring-loaded latch that operates as a conformational transducer. We also found that, at moderate ionic strengths, enHD changes conformation upon binding to cognate DNA. This change is of larger amplitude and somewhat orthogonal to the response to ionic strength. As a consequence, very high ionic strengths (e.g., 700 mM) block the electrostatic-spring-loaded latch and binding to cognate DNA becomes lock-and-key. However, the interplay between enHD conformation and cognate DNA binding is robust across a range of ionic strengths (i.e., 45 to 300 mM) that covers the physiologically-relevant conditions. Therefore, our results demonstrate the presence of a mechanism for the conformational control of cognate DNA recognition on a eukaryotic DBD. This mechanism can function as a signal transducer that locks the DBD in place upon encountering the cognate site during active DNA scanning. The electrostatic-spring-loaded latch of enHD can also enable the fine control of DNA recognition in response to transient changes in local ionic strength induced by variate physiological processes. 

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