Zhiming Chen

Bio: Zhiming Chen is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: Membrane curvature & Endocytosis. The author has an hindex of 8, co-authored 17 publications receiving 248 citations. Previous affiliations of Zhiming Chen include University of Pennsylvania.

Evolving models for assembling and shaping clathrin-coated pits.

Abstract: Clathrin-mediated endocytosis occurs via the assembly of clathrin-coated pits (CCPs) that invaginate and pinch off to form clathrin-coated vesicles (CCVs). It is well known that adaptor protein 2 (AP2) complexes trigger clathrin assembly on the plasma membrane, and biochemical and structural studies have revealed the nature of these interactions. Numerous endocytic accessory proteins collaborate with clathrin and AP2 to drive CCV formation. However, many questions remain as to the molecular events involved in CCP initiation, stabilization, and curvature generation. Indeed, a plethora of recent evidence derived from cell perturbation, correlative light and EM tomography, live-cell imaging, modeling, and high-resolution structural analyses has revealed more complexity and promiscuity in the protein interactions driving CCP maturation than anticipated. After briefly reviewing the evidence supporting prevailing models, we integrate these new lines of evidence to develop a more dynamic and flexible model for how redundant, dynamic, and competing protein interactions can drive endocytic CCV formation and suggest new approaches to test emerging models.

The N-Terminal Amphipathic Helix of Endophilin Does Not Contribute to Its Molecular Curvature Generation Capacity.

Abstract: N-BAR proteins such as endophilin are thought to bend lipid membranes via scaffolding (the molding of membranes through the crescent protein shape) and membrane insertion (also called wedging) of amphipathic helices. However, the contributions from these distinct mechanisms to membrane curvature generation and sensing have remained controversial. Here we quantitatively demonstrate that the amphipathic N-terminal H0 helix of endophilin is important for recruiting this protein to the membrane, but does not contribute significantly to its intrinsic membrane curvature generation capacity. These observations elevate the importance of the scaffolding mechanism, rather than H0 insertion, for the membrane curvature generation by N-BAR domains. Furthermore, consistent with the thermodynamically required coupling between curvature generation and sensing, we observed that the H0-truncated N-BAR domain is capable of sensing membrane curvature. Overall, our contribution clarifies an important mechanistic controversy i...

Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles.

Abstract: Nanoparticle science is rapidly changing the landscape of various scientific fields and defining new technological platforms. This is perhaps even more evident in the field of nanomedicine whereby nanoparticles have been used as a tool for the treatment and diagnosis of many diseases. However, despite the tremendous benefit conferred, common pitfalls of this technology is its potential short and long-term effects on the human body. To understand these issues, many scientific studies have been carried out. This review attempts to shed light on some of these studies and its outcomes. The topics that were examined in this review include the different possible uptake pathways of nanoparticles and intracellular trafficking routes. Additionally, the effect of physicochemical properties of nanoparticle such as size, shape, charge and surface chemistry in determining the mechanism of uptake and biological function of nanoparticles are also addressed.

Membrane curvature in cell biology: An integration of molecular mechanisms

Abstract: Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists.

Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine

Abstract: Nanoparticles (NPs) have attracted considerable attention in various fields, such as cosmetics, the food industry, material design, and nanomedicine. In particular, the fast-moving field of nanomedicine takes advantage of features of NPs for the detection and treatment of different types of cancer, fibrosis, inflammation, arthritis as well as neurodegenerative and gastrointestinal diseases. To this end, a detailed understanding of the NP uptake mechanisms by cells and intracellular localization is essential for safe and efficient therapeutic applications. In the first part of this review, we describe the several endocytic pathways involved in the internalization of NPs and we discuss the impact of the physicochemical properties of NPs on this process. In addition, the potential challenges of using various inhibitors, endocytic markers and genetic approaches to study endocytosis are addressed along with the principal (semi) quantification methods of NP uptake. The second part focuses on synthetic and bio-inspired substances, which can stimulate or decrease the cellular uptake of NPs. This approach could be interesting in nanomedicine where a high accumulation of drugs in the target cells is desirable and clearance by immune cells is to be avoided. This review contributes to an improved understanding of NP endocytic pathways and reveals potential substances, which can be used in nanomedicine to improve NP delivery.

What is a Human

Abstract: As we enter the Post-Human age many of our beliefs become redundant—not least the belief in human being.