Conspectus
Biomolecular self-assembly is a ubiquitous occurrence
in nature
that gives rise to sophisticated superstructures that enable the implementation
of complex biological functions. It encompasses both ordered structures,
such as the DNA double helix, and disordered structures, such as the
nucleolus and other nonmembranous organelles. In contrast to these
highly organized ordered structures, which exhibit specific patterns
or symmetry, disordered structures are characterized by their flexible
and randomized molecular organization, which provides versatility,
dynamicity, and adaptability to biological systems and contributes
to the complexity and functionality of living organisms. However,
these disordered structures usually exist in a thermodynamically metastable
state. This means that these disordered structures are unstable and
difficult to observe due to their short existence time. Achieving
disordered structures through precise control of the assembly process
and ensuring their stability and integrity pose significant challenges.
Currently, ongoing research efforts are focused on the self-assembly
of proteins with intrinsically disordered regions (IDRs). However,
the structural complexity and instability of proteins present prohibitive
difficulties in elucidating the multiscale self-assembly process.
Therefore, simple peptides, as a segment of proteins, hold great promise
in constructing self-assembly systems for related research. Since
our finding on droplet-like disordered structures that occur transiently
during the peptide self-assembly (PSA), our research is centered around
the dynamic evolution of peptide supramolecular systems, particularly
the modulation of a variety of assembled structures ranging from ordered
to disordered.
In this Account, we narrate our recent research
endeavors on supramolecular
structures formed by PSA, spanning from ordered structures to disordered
structures. We delve into the mechanisms of structural regulation,
shedding light on how these peptide-based structures can be controlled
more precisely. Moreover, we emphasize the functional applications
that arise from these structures. To begin, we conduct a comprehensive
overview of various types of ordered structures that emerge from PSA,
showcasing their diverse applications. Following, we elaborate on
the discovery and development of droplet-like disordered structures
that arise during PSA. A mechanistic study on multistep self-assembly
processes mediated by liquid–liquid phase separation (LLPS)
is critically emphasized. Ordered structures with different morphologies
and functions can be obtained by subtly controlling and adjusting
the metastable liquid droplets. In particular, we have recently developed
solid glasses with long-range disorder, including noncovalent biomolecular
glass based on amino acid and peptide derivatives, as well as high-entropy
glass based on cyclic peptides. This demonstrates the great potential
of using biologically derived molecules to create green and sustainable
glassy materials.