Electrostatically Controlled ex Situ and in Situ Polymerization of Diacetylene-Containing Peptide Amphiphiles in Living Cells

Abstract

Precise control of diacetylene-containing peptide amphiphile (DPA) based supramolecular architectures is important for their in cellulo polymerization behaviors and biomedical applications. Herein, we reported two DPAs (cationic PA-NH 2 and zwitterionic PA-OH) with a similar molecular structure, which exhibited completely opposite polymerization behaviors in aqueous solution and living cells. Specifically, PA-NH 2 was unpolymerizable in aqueous solution but underwent in cellulo polymerization to respond to the intracellular microenvironment. On the contrary, zwitterionic PA-OH was polymerized in solution, rather than inside living cells. Based on the results of cell viability and total internal reflection fluorescent microscopy measurement, PA-OH exhibited higher affinity with cell membranes and lower cytotoxicity than those of PA-NH 2 . Therefore, it is suggested that the in cellulo polymerization of PA-NH 2 should be responsive for greater cytotoxicity, rather than the membrane affinity. This study provides an in-depth understanding of the role of charge properties in the polymerization behavior of DPAs and seeks their potential biomedical applications.

Steric and Hydrophobic Control Over Sequence-Defined Peptide Templates to Modulate the Properties of Polydiacetylene Nanomaterials

“…Previous reports demonstrate the impact of diacetylene proximity to the peptide groups and differentiated the impact of amino acid sterics vs. charge on the morphology and absorption of PDA nanostructures. 15,23,27 This current work takes a deeper investigation on the ability of peptide templating groups to modulate PDA properties across lengths scales by molecularly controlling the geometry of peptide moieties through steric effects and hydrophobic interactions. In particular, the impact of these molecular characteristics on DA monomer assembly and the resulting polymer conformation will be mapped to photophysical and bulk electrical properties of adaptive PDA nanomaterials templated by the biomimetic interactions between the peptide segments.…”

“…Considering the widespread use of PDAbased materials in various biomedical applications nowadays, [17][18][19] there is a critical need for more studies that shed light on how to control material function based on molecular design of biologically relevant templating groups. [20][21][22][23][24][25][26] In this study, we systematically probe the interplay between molecular polarity (affecting hydrophobic interactions) and residue size (imparting steric effects) towards driving the assembly of diacetylene monomers and modulating the corresponding properties of PDAs (Figure 1).…”

Steric and Hydrophobic Control Over Sequence-Defined Peptide Templates to Modulate the Properties of Polydiacetylene Nanomaterials

“…Considering the widespread use of PDAbased materials in various biomedical applications nowadays, [18][19][20] there is a critical need for more studies that shed light on how to control material function based on the molecular design of biologically relevant templating groups. [21][22][23][24][25][26][27] In this study, we systematically probe the interplay between molecular polarity (affecting hydrophobic interactions) and residue size (imparting steric effects) towards driving the assembly of DA monomers and modulating the corresponding properties of PDAs (Figure 1). Previous reports demonstrated the impact of diacetylene proximity to the peptide groups and differentiate the impact of amino acid steric effect vs. charge on the morphology and absorption of PDA nanostructures.…”

“…Previous reports demonstrated the impact of diacetylene proximity to the peptide groups and differentiate the impact of amino acid steric effect vs. charge on the morphology and absorption of PDA nanostructures. 16,24,28 This current work takes a deeper investigation on the ability of peptide templating groups to modulate PDA properties across length scales by molecularly controlling the geometry of peptide moieties through steric effects and hydrophobic interactions. In particular, the impact of these molecular characteristics on DA monomer assembly and the resulting polymer conformation will be mapped to photophysical and electrical properties of adaptive PDA nanomaterials templated by the biomimetic interactions between the peptide segments.…”

Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions

“…Light as an ideal tool to manipulate cellular behaviors due to its unique characteristics of wide availability, gentle nature, low cost, and environmental friendliness can be tuned actively with high spatial and temporal resolution. , Most recently, photocontrolled supramolecular assembly/disassembly that regulates cellular behaviors has attracted much attention, such as bioadhesion, regenerative medicine, and targeted drug delivery . However, most of the light-triggered systems are restricted to the use of photolabile protecting groups (e.g., nitrobenzyl ester) and photochromic units (e.g., azobenzene, bisthienylethene), where the photocleavage or photocyclization reaction plays major roles. − Thus, the residue of the cleavage reaction or the oxygen consumption of the cyclization reaction can be harmful to living cells. Moreover, the response of these systems is relatively slow, and it is difficult to meet the needs of applications in living cells.…”