An Overview of Liquid-Liquid Phase Separation and Its Mechanisms in Sepsis

Meiling Cao,1,* Xinyi Zhang,2,* Xiaohan Wang,2,* Danyang Zhao,2 Mingyue Shi,2 Jiahui Zou,2 Lei Li,3 Hongkun Jiang2 1Department of Neonatology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 3Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongkun Jiang, Department of Pediatrics, The First Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, People’s Republic of China, Tel +86 02483282576, Email [email protected] Lei Li, Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, People’s Republic of China, Tel +86 02423896615, Email [email protected]: Sepsis is a systemic inflammatory response syndrome triggered by the invasion of bacteria or pathogenic microorganisms into the human body, which may lead to a variety of serious complications and pose a serious threat to the patient’s life and health. Liquid-liquid phase separation (LLPS) is a biomolecular process in which different biomolecules, such as proteins and nucleic acids, form liquid condensates through interactions, and these condensates play key roles in cellular physiological processes. LLPS may affect the development of sepsis through several pathways, such as modulation of inflammatory factors, immune responses, and cell death, by altering the function or activity of biomolecules, which, in turn, affect the cellular response to infection and inflammation. In this paper, we first discuss the mechanism of phase separation, then summarize the studies of LLPS in sepsis, and finally propose the potential application of LLPS in sepsis treatment strategies, while pointing out the limitations of the existing studies and the directions for future research.Keywords: biomolecular condensate, cGAS-STING, liquid-liquid phase separation, sepsis, inflammatory response