9 research outputs found
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Intrinsically disordered proteins access a range of hysteretic phase separation behaviors.
The phase separation behavior of intrinsically disordered proteins (IDPs) is thought of as analogous to that of polymers that undergo equilibrium lower or upper critical solution temperature (LCST and UCST, respectively) phase transition. This view, however, ignores possible nonequilibrium properties of protein assemblies. Here, by studying IDP polymers (IDPPs) composed of repeat motifs that encode LCST or UCST phase behavior, we discovered that IDPs can access a wide spectrum of nonequilibrium, hysteretic phase behaviors. Experimentally and through simulations, we show that hysteresis in IDPPs is tunable and that it emerges through increasingly stable interchain interactions in the insoluble phase. To explore the utility of hysteretic IDPPs, we engineer self-assembling nanostructures with tunable stability. These findings shine light on the rich phase separation behavior of IDPs and illustrate hysteresis as a design parameter to program nonequilibrium phase behavior in self-assembling materials
Micellar Self-Assembly of Recombinant Resilin-/Elastin-Like Block Copolypeptides
Reported
here is the synthesis of perfectly sequence defined, monodisperse
diblock copolypeptides of hydrophilic elastin-like and hydrophobic
resilin-like polypeptide blocks and characterization of their self-assembly
as a function of structural parameters by light scattering, cryo-TEM,
and small-angle neutron scattering. A subset of these diblock copolypeptides
exhibit lower critical solution temperature and upper critical solution
temperature phase behavior and self-assemble into spherical or cylindrical
micelles. Their morphologies are dictated by their chain length, degree
of hydrophilicity, and hydrophilic weight fraction of the ELP block.
We find that (1) independent of the length of the corona-forming ELP
block there is a minimum threshold in the length of the RLP block
below which self-assembly does not occur, but that once that threshold
is crossed, (2) the RLP block length is a unique molecular parameter
to independently tune self-assembly and (3) increasing the hydrophobicity
of the corona-forming ELP drives a transition from spherical to cylindrical
morphology. Unlike the self-assembly of purely ELP-based block copolymers,
the self-assembly of RLP–ELPs can be understood by simple principles
of polymer physics relating hydrophilic weight fraction and polymer–polymer
and polymer–solvent interactions to micellar morphology, which
is important as it provides a route for the de novo design of desired
nanoscale morphologies from first principles
Phase Behavior and Self-Assembly of Perfectly Sequence-Defined and Monodisperse Multiblock Copolypeptides
This paper investigates
how the properties of multiblock copolypeptides
can be tuned by their block architecture, defined by the size and
distribution of blocks along the polymer chain. These parameters were
explored by the precise, genetically encoded synthesis of recombinant
elastin-like polypeptides (ELPs). A family of ELPs was synthesized
in which the composition and length were conserved while the block
length and distribution were varied, thus creating 11 ELPs with unique
block architectures. To our knowledge, these polymers are unprecedented
in their intricately and precisely varied architectures. ELPs exhibit
lower critical solution temperature (LCST) behavior and micellar self-assembly,
both of which impart easily measured physicochemical properties to
the copolymers, providing insight into polymer hydrophobicity and
self-assembly into higher order structures, as a function of solution
temperature. Even subtle variation in block architecture changed the
LCST phase behavior and morphology of these ELPs, measured by their
temperature-triggered phase transition and nanoscale self-assembly.
Size and morphology of polypeptide micelles could be tuned solely
by controlling the block architecture, thus demonstrating that when
sequence can be precisely controlled, nanoscale self-assembly of polypeptides
can be modulated by block architecture
Noncanonical Self-Assembly of Highly Asymmetric Genetically Encoded Polypeptide Amphiphiles into Cylindrical Micelles
Elastin-like polypeptides (ELPs) are a class of biopolymers consisting of the pentameric repeat (VPGαG)n based on the sequence of mammalian tropoelastin that display a thermally induced soluble-to-insoluble phase transition in aqueous solution. We have discovered a remarkably simple approach to driving the spontaneous self-assembly of high molecular weight ELPs into nanostructures by genetically fusing a short 1.5 kDa (XGy)z assembly domain to one end of the ELP. Classical theories of self-assembly based on the geometric mass balance of hydrophilic and hydrophobic block copolymers suggest that these highly asymmetric polypeptides should form spherical micelles. Surprisingly, when sufficiently hydrophobic amino acids (X) are presented in a periodic sequence such as (FGG)8 or (YG)8, these highly asymmetric polypeptides self-assemble into cylindrical micelles whose length can be tuned by the sequence of the morphogenic tag. These nanostructures were characterized by light scattering, tunable resistive pulse sensing, fluorescence spectrophotometry, and thermal turbidimetry, as well as by cryogenic transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS). These short assembly domains provide a facile strategy to control the size, shape, and stability of stimuli responsive polypeptide nanostructures