Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics.

Cell cycles, essential for biological function, have been investigated extensively. However, enabling a global understanding and defining a physical quantification of the stability and function of the cell cycle remains challenging. Based upon a mammalian cell cycle gene network, we uncovered the underlying Mexican hat landscape of the cell cycle. We found the emergence of three local basins of attraction and two major potential barriers along the cell cycle trajectory. The three local basins of attraction characterize the G1, S/G2, and M phases. The barriers characterize the G1 and S/G2 checkpoints, respectively, of the cell cycle, thus providing an explanation of the checkpoint mechanism for the cell cycle from the physical perspective. We found that the progression of a cell cycle is determined by two driving forces: curl flux for acceleration and potential barriers for deceleration along the cycle path. Therefore, the cell cycle can be promoted (suppressed), either by enhancing (suppressing) the flux (representing the energy input) or by lowering (increasing) the barrier along the cell cycle path. We found that both the entropy production rate and energy per cell cycle increase as the growth factor increases. This reflects that cell growth and division are driven by energy or nutrition supply. More energy input increases flux and decreases barrier along the cell cycle path, leading to faster oscillations. We also identified certain key genes and regulations for stability and progression of the cell cycle. Some of these findings were evidenced from experiments whereas others lead to predictions and potential anticancer strategies.cell cycle phases | cell cycle checkpoints | landscape | flux T he cell cycle is a series of events that take place in a cell leading to its replication and division. Studying the cell cycle process is essential for understanding cell growth, proliferation, development, and death (1-4). Cell cycle comprises several distinct phases: G1 phase (resting), S phase (synthesis), G2 phase (interphase), and M phase (mitosis). Activation of each phase is dependent on the proper progression and completion of the previous one, which can be monitored by cell cycle checkpoints. It is now believed that all proliferation, differentiation, and cell death processes are controlled by the underlying gene regulatory networks (5), which often involve many complex feedback loops (6). The complexity of the large regulatory networks for the cell cycle makes it difficult to understand the global natures and connections between the underlying network and the cell cycle process. Furthermore, in the cell, the intrinsic fluctuations from the finite number of molecules and extrinsic fluctuations from dynamical and inhomogeneous environments (7, 8) coexist. Therefore, stochastic approaches are often required to explore the nature of the underlying network of chemical reaction soups (9-14). The challenge is how to understand the global picture and physical principles for the stability and function of the cell cycle ...

As a two-dimensional (2D) material, molybdenum disulfide (MoS2) exhibits unique electronic and optical properties useful for a variety of optoelectronic applications including light harvesting. In this article, we review recent progress in the synthesis, properties and applications of MoS2 and related heterostructures. Heterostructured materials are developed to add more functionality or flexibility compared to single component materials. Our focus is on their novel properties and functionalities as well as emerging applications, especially in the areas of light energy harvesting or conversion. We highlight the correlation between structural properties and other properties including electronic, optical, and dynamic. Whenever appropriate, we also try to provide fundamental insight gained from experimental as well as theoretical studies. Finally, we discuss some current challenges and opportunities in technological applications of MoS2.