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Sullivan Group

Stimuli-responsive peptides: from drug delivery to artificial cells

Cells typically make their exterior barrier (known as the membrane) out of lipids. To replicate a similar functionality for ProteoCell, the Sullivan lab will create a membrane out of peptides (i.e.small synthetic proteins made of select repeating amino acid sequences). A key focus area in the Sullivan lab is the development of protein and peptide biomaterials whose structure and behavior change in response to stimulus application (e.g., temperature, light, enzyme exposure). By applying a stimulus, a peptide’s structure changes providing selective assembly/disassembly. Stimuli-responsive biomaterials are ideal for applications ranging from drug delivery to synthetic cells to biotechnology applications. In the context of the ProteoCel project, we are employing temperature-responsive peptide materials in new ways such that these peptides self-assemble to create a membrane around the ProteoCell cytoplasm. Here, we will be using conjugates of elastin-like and collagen-like peptides to achieve the desired temperature-responsiveness. The temperature-response will be tuned by modifying the amino acid sequence in their structure. In addition to responsive structural roles, the peptide-based membrane will work to scaffold functional proteins and provide additional control to molecule transfer into/out of ProteoCells.

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Members

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Millicent Sullivan

What excites you about ProteoCell?

I’m thrilled to be working with a team of diverse scientists and social scientists – this allows me to learn science in very new areas, and to consider different perspectives on how the research my lab does might be interesting and useful. I also love the ProteoCell project because I find our ProteoCell ‘building blocks’ - peptides and proteins utterly fascinating! These molecules are very tunable and they will self-assemble to create a wide variety of active materials. I love that the ProteoCell project allows me to think outside of my usual ‘box’ of drug delivery research.
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Christopher Domalewski

What other hobbies, interests, roles do you perform outside of 'Science’?:

Endurance running! I’m with a running club/fundraising team called Fred’s Team, organized by Memorial Sloan Kettering Cancer Center (MSKCC) in NYC, which raises money and awareness for cancer research. With them, I’ve run in some amazing marathons such as New York, Chicago, and Berlin! I highly recommend all of them! Furthermore, in my free time, I scuba dive, read as long of fiction novels I can find, cook excellent eggs (such as french omelettes and omurice), and produce/mix/listen to house music!
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Thermally mediated self-assembly and dissociative responsiveness of Elastin-like peptide-Collagen-like peptide (ELP-CLP) conjugates from hyperthermic or hypothermic temperature stimuli.

 

Top: transmission electron micrographs (TEM) of the ELP-CLP conjugate nanovesicles at different temperatures; the left image is 4°C, the middle is 25°C, and the right is 80°C. Scale bars are provided in the left bottom corner of each image and correspond to 100 nm, 50 nm, and 100nm for 4°C, 25°C, and 80°C respectively.

 

Middle and lower portion: schematic secondary structure representations of the ELP (red) and CLP (blue) conjugates at the different thermal conditions corresponding to the above TEM images.

 

Figure adapted from Dunshee, L.C., et al., Bioengineering and Translational Medicine, 5 (1), 14 (2020). DOI: 10.1002/btm2.10145.

For more information please visit:

https://www.sullivan.che.udel.edu/

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