Project Title: Role of Nanoparticles’ Mechanical Stiffness in Cell Uptake

Project Duration: May 23 – July 29, 2016 (10 weeks), 40 hours per week.

Project Mentors –

• Primary Faculty Mentor (Name, Affiliation, website and Email/Phone):

Xianqiao Wang, College of Engineering,

http://xqwang.engr.uga.edu   xqwang@uga.edu 706-542-6251

• Secondary Faculty Mentor (Name, Affiliation, website and Email/Phone):

Jin Xie, Department of Chemistry

http://xie.uga.edu/index.html   jinxie@uga.edu 706-542-1933

• Graduate Student/PostDoc mentors (Name, Affiliation and Email/Phone):

Liuyang Zhang, College of Engineering, lyzhang@uga.edu

Weizhong Zhang, Department of Chemistry, wezhang@uga.edu

Project Description: Stiff or rigid nanoparticles (NPs) have been extensively investigated for clinical diagnostics and therapeutics. Recent experiments have also provided convincing evidence on the importance of elastic deformation in cellular uptake of nanoparticles. For example, it has been found that macrophages are unable to phagocytose very soft targets, which has profound implications on the functioning of the immune system. Human immunodeficiency virus (HIV) and Murine leukaemia virus (MLV) particles regulate their mechanical properties at different stages of the life cycle through internal morphological reorganization; immature HIV particle are relatively stiff for budding out of a host while mature HIV particles are substantially softer for entry into a host. So far, relatively little attention has been devoted to the effects of elastic properties on cellular uptake of nanoparticle such as vesicles via computational simulation although several theoretical models have been proposed to understand the effect of elastic deformation of particles on cellular uptake from the perspective of adhesive wrapping of an elastic, deformable vesicle by a lipid membrane.

REU Student Role and Responsibility: The main target of this project is to develop computational models and perform a series of experimental validations to identify the role of nanoparticle’s mechanical stiffness in the cell uptake. The student will study the effect of the stiffness of coating ligand on the nanoparticle surface by tuning the types of coating polymers on its penetration efficiency and translocation time into cells via an integrated computational and experimental methodology, therefore providing useful clues to understand the fundamental role of mechanical stiffness in the cell-nanoparticle interactions.

Expected Outcome for REU student: The primary goal for this project is the development of a manuscript for submission to the biomechanical journal and later as the preliminary result for our next potential proposals to NSF or NIH. The REU student will be recognized as a coauthor.