Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines

Despanie, Jordan; Dhandhukia, Jugal; Hamm‐Alvarez, Sarah F.; MacKay, J. Andrew

doi:10.1016/j.jconrel.2015.11.010

Cited by 129 publications

(104 citation statements)

References 160 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…Hot and cold spins were performed over three rounds in which the last round was resolubilized in cold MilliQ water to obtain pure ELPs above 95%. 25 ELPs were frozen at −80°C and subsequently lyophilized. Aliquot's were resuspended in PBS prior to use.…”

Section: Construction Expression and Purification Of Elpsmentioning

confidence: 99%

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

et al. 2020

Self Cite

View full text Add to dashboard Cite

Abbreviations: A99, laminin α1 chain RGD-containing peptide (AGTFALRGDNPQG); A99-ELP-C, chemically conjugated CGG-A99 containing peptide to I30; A99-ELP-R, recombinant A99 fused to I30; ECM, extracellular matrix; ELP, elastin-like polypeptide; FOV, field of view; HDF, human dermal fibroblast; I30, elastin-like polypeptide with a sequence of (VPGIG) 30 ; LCST, lower critical solution temperature; MW, molecular weight; OD, optical density; RT, room temperature; T t , transition temperature. AbstractThe extracellular matrix (ECM) is comprised of a large network of proteins that are essential for tissue development and repair. A bioactive RGD-containing peptide from laminin α1 chain, A99 (AGTFALRGDNPQG), promotes strong cell attachment and has demonstrated utility in cell culture and tissue engineering. Various materials can be utilized as a scaffold for bioactive peptides; however, it may be advantageous to design materials that use bioconjugation strategies that do not affect bioactivity, generate homogenous products, and can be produced at scale. This report is the first to compare the methods for preparing chemically conjugated and recombinant A99 to elastin-like polypeptides (ELPs) as the scaffold and characterize the biological and cell attachment activity using human dermal fibroblasts (HDFs). ELPs are biocompatible protein-polymers that are also thermo-responsive. Below a lower critical solution temperature (LCST), they are highly soluble. Above the LCST, ELPs phase separate into a polymer-rich liquid, known as a coacervate. Both chemically conjugated and recombinant fusion between A99 and an ELP (A99-ELP-R) show dose-dependent cell attachment. In addition, coating above the LCST provides better cell spreading compared to coating at 4°C. ELPs provide an excellent structural framework for deposition of bioactive peptides of the ECM, and their intrinsic biophysical properties make laminin peptide-ELPs promising biomaterials for cell culture and tissue engineering. K E Y W O R D S biomaterial, elastin-like polypeptide, laminin peptide, synthetic biology, tissue engineering 6730 | TRUONG eT al.

show abstract

Section: Construction Expression and Purification Of Elpsmentioning

confidence: 99%

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Concerted efforts have been made to identify attractive aquatic repeat proteins in terms of their molecular properties and biological functions, which are then used to explore their molecular basis and functional role for designing novel biomaterials . For example, elastin‐like polypeptides (ELPs), as a genetically engineered class of ‘protein polymers’ derived from human tropoelastin, can be assembled into 3D structures with precise control over mechanical properties . Such proteins and peptide motifs have been involved in the structural rigidity and functional diversity of resultant biomaterials.…”

Section: Engineering a 3d Home For Cell Accommodationmentioning

confidence: 99%

Engineering a Cell Home for Stem Cell Homing and Accommodation

Yin

et al. 2017

Adv. Biosys.

View full text Add to dashboard Cite

Distilling complexity to advance regenerative medicine from laboratory animals to humans, in situ regeneration will continue to evolve using biomaterial strategies to drive endogenous cells within the human body for therapeutic purposes; this approach avoids the need for delivering ex vivo‐expanded cellular materials. Ensuring the recruitment of a significant number of reparative cells from an endogenous source to the site of interest is the first step toward achieving success. Subsequently, making the “cell home” cell‐friendly by recapitulating the natural extracellular matrix (ECM) in terms of its chemistry, structure, dynamics, and function, and targeting specific aspects of the native stem cell niche (e.g., cell–ECM and cell–cell interactions) to program and steer the fates of those recruited stem cells play equally crucial roles in yielding a therapeutically regenerative solution. This review addresses the key aspects of material‐guided cell homing and the engineering of novel biomaterials with desirable ECM composition, surface topography, biochemistry, and mechanical properties that can present both biochemical and physical cues required for in situ tissue regeneration. This growing body of knowledge will likely become a design basis for the development of regenerative biomaterials for, but not limited to, future in situ tissue engineering and regeneration.

show abstract

“…A small increase (~1 °C) in temperature stimulates elastin-like polypeptides (ELPs) to phase separate, and this process can be fully reversed by decreasing the temperature. ELPs have been explored for drug delivery [15, 16] and tissue engineering [17]; however, they have untapped potential as biological tools with applications in synthetic biology. When expressed within cells and fused to key effector or fluorescent proteins, ELPs assemble cytosolic microdomains in a temperature dependent manner that can be tuned to target intracellular processes such as clathrin-mediated endocytosis [14, 18, 19].…”

Section: Introductionmentioning

confidence: 99%

A new temperature-dependent strategy to modulate the epidermal growth factor receptor

Tyrpak

Park

et al. 2018

Biomaterials

Self Cite

View full text Add to dashboard Cite

The dynamic manipulation of kinases remains a major obstacle to unraveling cell-signaling networks responsible for the activation of biological systems. For example, epidermal growth factor (EGF) stimulates the epidermal growth factor receptor (EGFR/ErbB1); however, EGF also recruits other kinases (HER2/ErbB2) involved with various signaling pathways. To better study EGFR we report a new strategy to selectively activate receptor tyrosine kinases fused to elastin-like polypeptides (ELPs), which can be visualized inside mammalian cells using fixed and live-cell fluorescence microscopy. ELPs are high molecular weight polypeptides that phase separate abruptly upon heating. When an EGFR-ELP fusion is heated, it clusters, initiates receptor internalization, phosphorylates, initiates downstream kinase signaling, and undergoes retrograde transport towards the cell body. Unlike other strategies to block EGFR (small molecule inhibitors, RNAi, or transcriptional regulators), EGFR-ELP clustering can be specifically switched on or off within minutes. Live-cell imaging suggests that EGFR-ELPs assemble in most cells with only a 3 °C increase in temperature. This strategy was found reversible and able to dynamically control the downstream phosphorylation/activation of the ERK1/2 pathway. For the first time, this strategy enables the rational engineering of specific temperature-sensitive receptors that may have broad applications in the study and manipulation of biological processes.

show abstract

Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines

Cited by 129 publications

References 160 publications

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

Engineering a Cell Home for Stem Cell Homing and Accommodation

A new temperature-dependent strategy to modulate the epidermal growth factor receptor

Contact Info

Product

Resources

About