In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence. MDPs with histidine residues within the hydrophobic face disassemble below physiological pH and form nanofibers at higher pH. Taking advantage of their stimulus-triggered behavior, an anti-PD-1 antibody was loaded into histidine MDP hydrogels to examine pH-dependent differences in payload delivery in vitro. Hydrogels composed of MDPs with histidine on the hydrophilic face demonstrated pH-dependent payload retention. Additionally, they showed significantly slower antibody release and reduced antibody diffusion rates in vitro compared to MDP hydrogels lacking histidine.

Hypothesis

Phospholipids are widely used in food and pharmacological formulations. However, these typically suffer from limitations such as low colloidal stability. Promising stability has been observed for vesicles based on phosphatidylglucose (P-Glu), but fundamental knowledge on this lipid is missing and those observations were made using P-Glu containing mixed acyl groups. The acyl groups are expected to influence the properties of phosphatidylglucose to a large extent.

Experiments

Using an enzyme-based method, P-Glu containing either palmitic (DPP-Glu), stearic (DSP-Glu) or oleic (DOP-Glu) acid were synthesized. The morphology of the lipid dispersions was studied using small angle x-ray scattering and cryogenic transmission electron microscopy and the data was modelled to extract bilayer structural parameters. Phosphatidylcholine lipids containing the same fatty acids were studied for comparison.

Findings

All phosphatidylcholine lipids formed mainly multilamellar vesicles. DOP-Glu formed unilamellar vesicles (ULVs), while disc like objects were observed in the case of DPP-Glu and DSP-Glu formed predominantly bilayer stacks. In the 1:1 mixture of the DOPC and DOP-Glu, ULVs were formed. The bilayer thickness increased as follows: DOP-Glu < DPP-Glu < DSP-Glu and in the PC series the same trend was seen for the lamellar spacing. DSP-Glu had similar lamellar spacing as DSPC.

Investigation of the dynamics of colloids in bulk can be hindered by issues such as multiple scattering and sample opacity. These challenges are exacerbated when dealing with inorganic materials. In this study, we employed a model system of Akaganeite colloidal rods to assess three leading dynamics measurement techniques: 3D-(depolarized) dynamic light scattering (3D-(D)DLS), polarized-differential dynamic microscopy (P-DDM), and x-ray photon correlation spectroscopy (XPCS). Our analysis revealed that the translational and rotational diffusion coefficients captured by these methods show a remarkable alignment. Additionally, by examining the q-ranges and maximum volume fractions for each approach, we offer insights into the best technique for investigating the dynamics of anisotropic systems at the colloidal scale.

Sterols have played an important role in membrane evolution. The effect of these molecules, particularly the naturally occurring ones, such as cholesterol, ergosterol, lanosterol, phytosterols and oxysterols on the prop-erties of lipid model membranes have been extensively investigated. Unfortunately, other naturally occurring sterols such as desmosterol and lathosterol have received very little attention. Using small angle X-ray scattering (SAXS), we have carried out detailed investigations on the influence of desmosterol and lathosterol along with coprostanol on the phase behaviour of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes. SAXS results indicate both that these sterols modulate the properties of the DPPC bilayer in a manner similar to cholesterol. However, we have found desmosterol to be more efficient than cholesterol in suppressing the main transition of DPPC, with the fluid phase stabilized at around 15 mol% (compared to around 20 mol% in cholesterol). Coprostanol on the other hand was found to be less efficient in stabilizing the fluid phase than the other two. The results obtained from our study in combination with those existing in the literature will help in establishing a complete picture of how different sterols influence the properties of lipid membranes.