Micelle Density Regulated by a Reversible Switch of Protein Secondary Structure

Sallach, Rory E.; Wei, Min; Biswas, Nilanjana; Conticello, Vincent P.; Lecommandoux, Sébastien; Dluhy, Richard A.; Chaikof, Elliot L.

doi:10.1021/ja0638509

Cited by 96 publications

(79 citation statements)

References 40 publications

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“…Second, ELPs are not solely responsive to temperature; the phase transition of ELPs can also be triggered by ionic strength, pH and light29 , 32 . However, the use of these triggers in the context of self-assembly, as opposed to coacervation 33 , only has a few precedents 11,34,35 . We emphasize that for such systems to move beyond proof-ofprinciple and be useful in the emerging field of nanomedicine, triggered self-assembly by physiologically relevant triggers is essential and, is thus, the driving force behind this study.…”

Section: Introductionmentioning

confidence: 99%

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

et al. 2007

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We report herein thermally responsive elastin-like polypeptides (ELPs) in a linear AB diblock architecture with an N-terminal peptide ligand that self-assemble into spherical micelles when heated slightly above body temperature. A series of 10 ELP block copolymers (ELP BC s) with different molecular weights and hydrophilic-to-hydrophobic block ratios were genetically synthesized by recursive directional ligation. The self-assembly of these polymers from unimers into micelles was investigated by light scattering, fluorescence spectroscopy and cryo-TEM. These ELP BC s undergo two phase transitions as a function of solution temperature: a unimer to spherical micelle transition at an intermediate temperature, and a micelle to bulk aggregate transition at a higher temperature when the hydrophilic-to-hydrophobic block ratio is between 1:2 and 2:1. The critical micelle temperature is controlled by the length of the hydrophobic block and the size of the micelle is controlled by both the total ELP BC length and hydrophilic-to-hydrophobic block ratio. These polypeptide micelles display a critical micelle concentration in the range of 4-8 μM demonstrating high stability of these structures. These studies have also identified a subset of ELP BC s bearing terminal peptide ligands that are capable of forming multivalent spherical micelles that present multiple copies of the ligand on their corona in the clinically relevant temperature range of 37-42 °C and target cancer cells. These ELP BC s may be useful for drug targeting by thermally triggered multivalency. More broadly, the design rules uncovered by this study should be applicable to the design of other thermally reversible nanoparticles for diverse applications in medicine and biology.

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Section: Introductionmentioning

confidence: 99%

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

et al. 2007

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“…Recently, we have reported the synthesis of high molecular weight recombinant protein block copolymers using an approach, which affords significant flexibility in the selection and assembly of blocks of diverse size and structure. [7][8][9][10][11] This has led to the synthesis of a new class of BAB protein triblock copolymer composed of large polypeptide block sequences ranging from 400 to 1200 amino acids in length. This class of protein block copolymers are derived from elastin-mimetic polypeptide sequences in which identical endblocks of a hydrophobic, plastic-like sequence are separated by a central hydrophilic, elastomeric block.…”

Section: Introductionmentioning

confidence: 99%

Deformation Responses of a Physically Cross-Linked High Molecular Weight Elastin-Like Protein Polymer

Sallach

Caves

et al. 2008

Biomacromolecules

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Recombinant protein polymers were synthesized and examined under various loading conditions in order to assess the mechanical stability and deformation responses of physically crosslinked, hydrated, protein polymer networks designed as triblock copolymers with central elastomeric and flanking plastic-like blocks. Uniaxial stress-strain properties, creep and stress relaxation behavior, as well as the effect of various mechanical preconditioning protocols on these responses were characterized. Significantly, we demonstrate for the first time that ABA triblock copolymers when redesigned with substantially larger endblock segments can withstand significantly greater loads. Furthermore, the presence of three distinct phases of deformation behavior was revealed upon subjecting physically crosslinked protein networks to step and cyclic loading protocols in which the magnitude of the imposed stress was incrementally increased over time. We speculate that these phases correspond to the stretch of polypeptide bonds, the conformational changes of polypeptide chains, and the disruption of physical crosslinks. The capacity to select a genetically engineered protein polymer that is suitable for its intended application requires an appreciation of its viscoelastic characteristics and the capacity of both molecular structure and conditioning protocols to influence these properties.

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“…Numerous studies of the behavior of amphiphilic multiblock ELRs have provided clear evidence for the tendency of such molecules to self-assembly into stable nano-and microparticles when the temperature is raised above the Tt of the polymer [121,122]. For example, Chilkoti's group has designed and synthesized a battery of ELRs that selfassemble into micelles in the presence of a physiologically relevant trigger, such as a hyperthermic temperature in the range 37 42ºC [123].…”

Section: Elr Self-assembly Into Spherical Particles For Drug Deliverymentioning

confidence: 99%

“…Numerous other studies have been published since then in an attempt to shed light on the self-assembly of such elastin-like micelles [122,123,157]. Other morphologies, such as vesicles, are much harder to obtain.…”

Section: Elr-based Nanostructuresmentioning

confidence: 99%

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

Arias¹,

Santos²,

Fernández‐Colino³

et al. 2014

CTMC

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Abstract:The emergence of the new scientific field known as nanomedicine is being catalyzed by multiple improvements in nanoscience techniques and significant progress in materials science, especially as regards the testing of novel and sophisticated biomaterials. This conjuncture has furthered the development of promising instruments in terms of detection, bioanalysis, therapy, diagnostics and imaging. Some of the most innovative new biomaterials are protein-inspired biomimetic materials in which modern biotechnology and genetic-engineering techniques complement the huge amount of information afforded by natural protein evolution to create advanced and tailor-made multifunctional molecules. Amongst these protein-based biomaterials, Elastin-like Recombinamers (ELRs) have demonstrated their enormous potential in the fields of biomedicine and nanoscience in the last few years. This broad applicability derives from their unmatched properties, particularly their recombinant and tailor-made nature, the intrinsic characteristics derived from their elastin-based origin (mainly their mechanical properties and ability to self-assemble as a result of their stimuli-responsive behavior), their proven biocompatibility and biodegradability, as well as their versatility as regards incorporating advanced chemical or recombinant modifications into the original structure that open up an almost unlimited number of multifunctional possibilities in this developing field. This article provides an updated review of the recent challenges overcome by using these recombinant biomaterials in the fields of nano-and biomedicine, ranging from nanoscale applications in surface modifications and self-assembled nanostructures to drug delivery and regenerative medicine.

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Micelle Density Regulated by a Reversible Switch of Protein Secondary Structure

Cited by 96 publications

References 40 publications

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles

Deformation Responses of a Physically Cross-Linked High Molecular Weight Elastin-Like Protein Polymer

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

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