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Download Undergraduate/Graduate Category: Interdisciplinary Topics, Centers and Institutes Degree Level:Graduate
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Undergraduate/Graduate Category: Interdisciplinary Topics, Centers and Institutes Degree Level:Graduate Abstract ID#1469 Introduction Experimental Results • Liposome is the most common vehicle for targeted drug delivery[1] Preliminary Solid-Mechanics Model Liposome geometry before and after fusion • Constituting lipids must be fine-tuned to specific optimal chemical and mechanical properties to effectively deliver cytotoxin to malignant tissues[2] Height: 64.4 um 132um 102.7um Assumptions: a) Boundary conditions: V = constant b) Free of intersurface forces: No adhesion c) Deformed geometry: truncated sphere with planar polar regions d) Mechanical response: F(z, a) reflects mechanical behavior of the liposome deformation-hemifusion-fusion • Quantitative mechanics of endocytosis or fusion of liposome with a cell or another liposome is rare in literature 160 um 173um Total Potential Energy Liposome on cantilever Liposome on mica Aggregated Configuration: Fused liposome on mica Liposome fusion process 400 Experiment Equipment Second Force-drop Hemi-fused Configuration: b 300 Liposome preparation d a Microfluidic device for liposome preparation [3] Applied force, F (nN) 200 d First Force-drop b 100 100 𝜇𝑚 a 0 c e e -100 Liposome fusion Compression c Fusion -200 Laser Hemi-fusion Tension Pre-fusion Conclusions and Future Work -300 0 20 40 60 80 100 Distance from cantilever to mica, D (um) 120 140 160 Characters of distinguished regions Liposome mica Region ab bc cd Behavior Gradual Instantaneous Gradual Process Reversible elastic deformation Irreversible Hemi-fusion: fusion of outer lipid layer Reversible deformation as F turns from tensile to compressive de Beyond e Instantaneous Gradual Irreversible fusion (coalescence) of liposomes Reversible elastic deformation • Liposome composed of lipid with neutral spontaneous curvature cannot fuse spontaneously in 50mM CaCl 2 solution at room temperature • Experiments were repeated for 56 times in identical conditions, liposome fusion was found in 5 of them microscopy Schematic diagram for liposome fusion equipment • 5 fusion processes present identical fusion pattern: hemi-fusion, fusion • In failed experiments, liposomes were observed to explode before fusing with external • Critical forces for DOPC liposome with diameter of 102.7mm hemi-fusion and fusion are 61.9nN and 258.9nN, respectively; critical membrane tension for hemi-fusion is 0.72mN/m based on solid-mechanics model • For the future work, new material will be introduced into DOPC, in order to produce liposome with negative effective spontaneous curvature and critical forces and membrane tensions will be obtained. Acknowledge • This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. CMMI-#1232046 • Thanks to Yuting Huang from Harvard for suggestions on sample preparation References [1] Torchilin, VP; “Multifunctional Nanocarriers”; Adv Drug Deliv Rev 2006 Dec; 58 (14): 1532-1555; [2] Jason, HS; Anne, LV; etc. “Enabling Individualized Therapy through Nanotechnology”; Pharmacol Res 2010 Aug; 62(2): 57-89 [3] Laura, RA; Sujit, SD; Shin-Hyun, K; Esther, A; Thomas, EK; Francisco, M; David AW; “ Ultrathin Shell Double Emulsion Templated Giant Unilamellar Lipid Vesicles with Controlled Microdomain Formation”; Small 2014 Oct; 10(5): 950-956;
