Triggered Self-Sorting of Peptides to Form Higher-Order Assemblies in a Living System

Abstract

Biological components (protein, DNA, lipid rafts, etc.) self-sort to form higher-order structures with elegant modulation by endogenous stimuli for maintaining cellular functions in living cells. However, the challenge of producing self-sorted higher-order assemblies of peptides in living systems (cells and tissues) spatiotemporally has yet to be achieved. This work reports the using of a biocompatible strategy to construct self-sorted assemblies of peptides in living cells and tumorbearing mice. The results show that the designed peptides selfsort to form distinct nanostructures in living cancer cells using an endogenous trigger, as evidenced by confocal laser scanning microscopy and Bio-EM. Wound-healing experiments indicate that the in situ generation of self-sorted nanostructures exhibits a synergistic effect that significantly decreases the migration of cancer cells. In vivo experiments demonstrate that the designed peptides could self-sort in tumor-bearing mice and improve the tumor penetrating ability of the impenetrable component in tumor tissue. We can further program the formation of selfsorted materials through orthogonal triggers by introducing an exogenous trigger (light) and an endogenous trigger independently. Thus, this work provides a strategy to control multiple self-assembling processes in the context of the living system and provides a general strategy to construct self-sorted structures for the emergent properties of materials science.

Recognition of atomic-level difference in porphyrin dyads for self-sorted supramolecular polymer growth

“…2c). 16,19,20,40,41 The heating curves were fitted into the nucleation-elongation model to estimate the values of the elongation enthalpy (ΔH e ), critical elongation temperature (T e ), and equilibrium constant of the nucleation step (K a ) (Table S1 †). The estimated ΔH e s values did not change significantly over a wide range of concentrations.…”

“…This is primarily due to the necessity of topological selections to achieve self-sorting behavior. [13][14][15][16][17][18][19][20][21] For example, Hamachi et al investigated the self-sorting behavior of two different gelators. The mixture of the two gelators resulted in a self-sorted double network owing to the considerable difference in the driving forces for the self-assembly of each gelator.…”

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions

“…Constructing non-natural macromolecules with prolonged retention inside cells to regulate a variety of physiological activities has attracted tremendous scientific interest. [1][2][3][4][5][6] Although the biosynthesis of peptide polymers, supramolecular self-assemblies and two-dimensional materials has been performed in human cells and living organisms by noncovalent bonding, [7][8][9][10] building larger-sized materials based on covalent bonding remains a significant challenge. Artificial-mediated chemical reactions such as free radical photo-polymerization, [11] halogenalkyne coupling, [12] metalfree azide-alkyne cycloaddition, [13][14][15] metal carbene reaction, [16] aniline coupling, [17] and oxidative polymerization [18] have been applied to control cancer cell fate, to modulate biological functions, and for targeted biological analysis.…”

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions

“…Constructing non-natural macromolecules with prolonged retention inside cells to regulate a variety of physiological activities has attracted tremendous scientific interest. [1][2][3][4][5][6] Although the biosynthesis of peptide polymers, supramolecular self-assemblies and two-dimensional materials has been performed in human cells and living organisms by noncovalent bonding, [7][8][9][10] building larger-sized materials based on covalent bonding remains a significant challenge. Artificial-mediated chemical reactions such as free radical photo-polymerization, [11] halogenalkyne coupling, [12] metalfree azide-alkyne cycloaddition, [13][14][15] metal carbene reaction, [16] aniline coupling, [17] and oxidative polymerization [18] have been applied to control cancer cell fate, to modulate biological functions, and for targeted biological analysis.…”

“…Living cells, because of their highly complex chemical environment, can be used as remarkable integrated laboratories. Constructing non‐natural macromolecules with prolonged retention inside cells to regulate a variety of physiological activities has attracted tremendous scientific interest [1–6] . Although the biosynthesis of peptide polymers, supramolecular self‐assemblies and two‐dimensional materials has been performed in human cells and living organisms by noncovalent bonding, [7–10] building larger‐sized materials based on covalent bonding remains a significant challenge.…”