Research | Liu Lab

Current research interests

1. Multidimensional Characterization of Cellular Mechanical Forces at the molecular level

（细胞机械力的多维度表征）

In tissues, cells exhibit dynamic behavior and their activities are perpetually influenced by a variety of mechanical forces. These forces arise from the interactions with neighboring cells and the extracellular matrix (ECM), involving actions like pushing, pulling, and compressing. The mechanical forces exerted by cells within tissues are significant, often reaching several nanoNewtons (nN). However, the force exerted on each receptor is quite small, typically ranging from a few picoNewtons (pN) to several tens of pN. Despite their minute size, these molecular-level forces play a crucial role in precisely regulating signal transduction both temporally and spatially. This regulation is vital as it directly or indirectly influences various biological processes, including cell differentiation, gene expression, and apoptosis.

组织中的细胞是高度动态的，它们的功能不断受到其他细胞和细胞外基质（ECM）通过推、拉和挤压产生的各种形式的机械力的调节。细胞在组织中产生的机械力是巨大的，可轻松达到数 nN 的范围。相反，每个受体所受的力很小，其大小分布在几个 pN 到几十个 pN 之间，但这些分子力可以在时间和空间上精确调节信号转导过程，从而直接或间接地控制细胞分化、基因表达和细胞凋亡等一系列生物反应。

我们的研究小组致力于从分子水平表征细胞机械力。通过开发新型分子机械传感器技术（如基于 DNA 的荧光张力探针），我们在单个蛋白水平上精确测量并可视化细胞膜上的机械力传递过程。这些探针能够测量从几皮米牛顿（pN）到几十皮米牛顿的力，揭示了细胞如何利用微观机械信号影响胚胎发育、肿瘤迁移和免疫识别等关键生物过程。

Reversible shearing DNA-based tension probe and cellular force images

Reference: Li et al, A Reversible shearing DNA probe for visualizing mechanically strong receptors in living cells, Nature Cell Biology, 2021.

https://www.nature.com/articles/s41556-021-00691-0.

Movie: Imaging of different levels of integrin force in real time with multiplexed RSDTP.

2. Rigidity Sensing and Cancer Immunology (细胞刚性响应与肿瘤免疫)

This research direction focuses on utilizing molecular tension probes to understand cellular responses to the rigidity of the extracellular matrix at the molecular level. The objective is to reveal how different cell types (such as fibroblasts, cancer cells, and T cells) perceive and respond to the stiffness of their environment through distinct mechanical strategies. These studies provide a new perspective in understanding the mechanisms of cellular rigidity sensing and mechanical signal transduction. Especially in the context of tumor growth and spread, our research aims to elucidate the interactions between cancer cells and immune cells, deepening our understanding of the tumor microenvironment. By investigating how T cells, which play a crucial role in tumor immunity, respond mechanically to and combat cancer cells, we hope to inform the development of novel immunotherapeutic strategies. Our research is expected to optimize existing immunotherapy methods like CAR-T cell therapy by better understanding T cell behavior in the tumor microenvironment, offering new insights for targeted immunotherapies.

主要集中于利用先进的分子力学传感器技术，深入探索细胞对细胞外基质刚度的响应机制。我们的目标是揭示不同类型细胞，特别是肿瘤细胞和免疫细胞，如何通过独特的力学策略感知并适应其所处的微环境。这些研究对于理解细胞如何通过机械信号调节其行为具有重要意义，特别是在肿瘤生长和扩散的背景下。

通过深入研究细胞如何响应周围环境的机械特性，我们希望能够揭示肿瘤细胞与免疫细胞之间的相互作用，并进一步理解肿瘤微环境的复杂性。例如，我们的研究聚焦于T细胞，这类免疫细胞在肿瘤免疫中扮演着至关重要的角色。我们探索T细胞如何通过机械信号感知并对抗肿瘤细胞，这对开发新型的免疫治疗策略至关重要。我们的研究结果预期将有助于优化现有的免疫治疗方法，例如CAR-T细胞疗法，通过更好地理解T细胞在肿瘤微环境中的行为，为针对性的免疫疗法提供新的思路。

总之，通过在细胞机械力表征方面的先进研究，我们期望为肿瘤生物学和免疫学领域贡献重要的见解，推动对肿瘤免疫相互作用更深层次的理解，从而为临床免疫治疗提供新的策略和方向。

Reference: Wenxu Wang etal, Nature Methods, 2023,
https://doi.org/10.1038/s41592-023-02037-0