Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy

Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy(AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

Biological Interaction and Imaging of Ultrasmall Gold Nanoparticles

Ultrasmall gold nanoparticles(AuNPs)typically includes atomically precise gold nanoclusters(AuNCs)and AuNPs with a core size below 3 nm.Serving as a bridge between small molecules and traditional inorganic nanoparticles,the ultrasmall AuNPs show the unique advantages of both small molecules(e.g.,rapid distribution,renal clearance,low non-specific organ accumulation)and nanoparticles(e.g.,long blood circulation and enhanced permeability and retention effect).The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis,monitoring and treatment.Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs,this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs.We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs.We then discuss the organ interactions,especially focus on the interactions of the liver and kidneys.We further present the recent advances in the tumor interactions of ultrasmall AuNPs.In addition,the imaging performance of the ultrasmall AuNPs is summarized and discussed.Finally,we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs,aiming to accelerate their clinical translation.

Analytical design of effective thermal conductivity for fluid-saturated prismatic cellular metal honeycombs

A comparative optimal design of fluid-saturated prismatic cellular metal honeycombs （PCMHs） having different cell shapes is presented for thermal management applications. Based on the periodic topology of each PCMH, a unit cell （UC） for thermal transport analysis was selected to calculate its effective thermal conductivity. Without introducing any empirical coefficient, we modified and extended the analytical model of parallel-series thermal-electric network to a wider porosity range （0.7 ~ 0.98） by considering the effects of two-dimensional local heat conduction in solid ligaments inside each UC. Good agreement was achieved between analytical predictions and numerical simulations based on the method of finite volume. The concept of ligament heat conduction efficiency （LTCE） was proposed to physically explain the mechanisms underlying the effects of ligament configuration on effective thermal conductivity （ETC）. Based upon the proposed theory, a construct strategy was developed for designing the ETC by altering the equivalent interaction angle with the direction of heat flow： relatively small average interaction angle for thermal conduction and relatively large one for thermal insulation.

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular ＆ Molecular Immunology. 2008;5（4）：261-269.

Amino acids essential for the interaction between cellular heat shock protein 90 and a Kaposi's sarcoma-associated herpesvirus-encoded protein kinase ORF36

Dear Editor,Protein-protein interactions（PPIs）often play important roles in biological processes（Zhang et al.,2016）.The split Renilla luciferase complementation assay（SRLCA）is one of the methods in studying PPIs.SRLCA is based on the complementation of the N-terminal domains of Renilla luciferase（LN）and C-terminal domains of Renilla luciferase （LC） non-functional halves of Renilla luciferase fused to possibly interacting proteins and emit luminescence （Deng et al., 2011; Jiang et al., 2010） （Supplementary Figure S1A）.

Multi-walled carbon nanotubes reversing the bone formation of bone marrow stromal cells by activating M2 macrophage polarization

Multi-walled carbon nanotubes(MWCNTs)are an excellent bone tissue repair material both in vitro and in vivo.The interactions between MWCNTs and single type of cells of bone tissue,including osteoblasts,bone marrow stromal cells(BMSCs)or osteoclasts,have been extensively studied.However,the interactions between MWCNTs with different types of cells in the bone microenvironment remain elusive.Bone microenvironment is a complex system composed of different types of cells,which have interactions between each other.In this work,the effects of MWCNTs on bone microenvironment were firstly studied by culture of MWCNTs with BMSCs,osteoblasts,osteoclasts,macrophages and vascular endothelial cells,respectively.Then,co-culture systems of macrophages-BMSCs,macrophages-calvaria and macrophages-BMSCs-vascular endothelial cells were treated with MWCNTs,respectively.The osteogenic differentiation of BMSCs and osteoblasts was inhibited when these two types of cells were cultured with MWCNTs,respectively.Strikingly,when co-culture MWCNTs with BMSCs and macrophages,the osteogenesis of BMSCs was promoted by inducing the M2 polymerization of macrophages.Meanwhile,MWCNTs promoted the bone formation in the osteolysis model of calvaria ex vivo.In addition,the formation of osteoclasts was inhibited,and angiogenesis was increased when treated with MWCNTs.This study revealed the inconsistent effects of MWCNTs on single type of bone cells and on the bone microenvironment.The results provided basic research data for the application of MWCNTs in bone tissue repair.