Effect of amino acid composition of elastin‐like polypeptide nanoparticles on nonspecific protein adsorption, macrophage cell viability and phagocytosis

Abstract

Development of elastin‐like polypeptide (ELP) biomaterials is widespread, but information critical for clinical deployment is limited, with biocompatibility studies focused on a narrow cross‐section of ELP sequences. Macrophages can impair biomaterial systems by degrading or isolating the biomaterial and by activating additional immune functions. Their phagocytic response will reveal early immune biocompatibility of ELP nanoparticles (NPs). This study examines that response, induced by the adsorbed protein corona, as a function of ELP guest amino acid, chain length and NP diameter. The breadth of proteins adsorbed to ELP NPs varied, with valine‐containing ELP NPs adsorbing fewer types of proteins than leucine‐containing constructs. Particle diameter was also a factor, with smaller leucine‐containing ELP NPs adsorbing the broadest range of proteins. Macrophage viability was unaffected by the ELP NPs, and their phagocytic capabilities were unimpeded except when incubated with a 500 nm valine‐containing 40‐mer. This NP significantly decreased the phagocytic capacity of macrophages relative to the control and to a corresponding 500 nm leucine‐containing 40‐mer. NP size and the proportion of opsonin to dysopsonin proteins likely influenced this outcome. These results suggest that certain combinations of ELP sequence and particle size can result in an adsorbed protein corona, which may hinder macrophage function.

Fetuin‐A adsorption to tunable polydimethylsiloxane and subsequent macrophage response

“…42,43 Notably, the molecular weight of the fetuin-A and HSA used in these experiments are within a similar size range for proteins, at 49 kDa and 66 kDa, respectively. Given that fetuin-A and albumin are among the highest adsorbed proteins to biomaterials in various proteomic studies, 5,[12][13][14]44,45 it is interesting to see that from solutions of the same concentration, fetuin-A appears to adsorb in greater amounts. To date the literature on fetuin-A adsorbed to biomaterials is only from qualitative proteomic studies.…”

“…With the advancement of mass spectrometry based proteomics techniques, fetuin-A has appeared in numerous studies where it has frequently been one of the most highly adsorbed proteins on the biomaterial surface. [12][13][14] In their 2016 work, Vyner and Amsden explored this higher-thanexpected adsorption of fetuin-A, and identified it as the protein contributing to increased fibroblast proliferation on substrates with different chain flexibilities and thus different stiffness levels. 5 Polydimethylsiloxane (PDMS) is an organosilicon compound that can be formulated to produce a variety of surface moduli while maintaining surface topography and surface wettability.…”

“…Despite the recognized implications in the processes of calcium binding, insulin receptor inhibition, and inflammation, 10 there is relatively little known about the complete structure and function of fetuin‐A compared to other plasma proteins. With the advancement of mass spectrometry based proteomics techniques, fetuin‐A has appeared in numerous studies where it has frequently been one of the most highly adsorbed proteins on the biomaterial surface 12–14 . In their 2016 work, Vyner and Amsden explored this higher‐than‐expected adsorption of fetuin‐A, and identified it as the protein contributing to increased fibroblast proliferation on substrates with different chain flexibilities and thus different stiffness levels 5 …”