Prof. Liu has a long-standing interest in mechanobiology of biological membranes, looking at how physical forces and stimuli affect biological functions from the vantage point of membrane remodeling and protein machineries at the plasma membrane that respond to these cues.

In this context, he and his team have been investigating how membrane and cytoskeleton mechanics govern membrane remodeling during endocytosis and cell migration. His lab is also interested in building synthetic cells from biological parts from the bottom-up. In this context, he and his team have been engineering mechanosensitive synthetic cells for a range of biomedical applications.

Part of the lab focuses on investigating intracellular trafficking using various state of the art live cell imaging and super resolution fluorescence imaging techniques. They are particularly interested in clathrin-mediated endocytosis (CME), a process by which cells uptake proteins and other macromolecules by forming budded structures coated with clathrin on the plasma membrane. Various viruses, specifically viruses like Influenza A virus, SARS CoV-2, and HIV, can hijack CME and similar processes to gain access to the cell.

In their recent work, Prof. Liu's team investigated the role of epsin, a membrane bending protein, in enabling IAV entry via CME. It has been shown that upon IAV binding to the plasma membrane, epsin can specifically bind to cell surface ubiquitinated receptors. They showed that epsin’s interaction with proteins at the site of IAV binding initiated its membrane bending mechanism. Their findings show the ability of IAVs to hijack activity of membrane bending proteins to initiate membrane bending and receptor-mediated endocytosis for cellular entry.

Unlike traditional microscopy, lattice light sheet technique allowed us to visualize the viral entry on the entire cell surface. Furthermore, we were able to track IAVs before and after they attach to the cell membrane.

• This data was acquired on ZEISS Lattice Lightsheet 7 at the University of Michigan BRCF Microscopy Core Facility with the assistance of the core facility team.
  

Since the technique utilizes lattice light sheets which excite a thin region of the cell, they could reduce the background noise created by out-of-focus excited fluorescence proteins. This allowed the generation of high-quality viral particle tracks from which they could determine the amount of epsin and clathrin recruitment associated with the viruses. Light sheet microscopy also reduces the amount of photobleaching which enables the continuous imaging of cells for a longer period without compromising the signal quality.