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  3. Mimicking the process from secretory vesicles to organelles in eukaryotic cell evolution by clustering enzyme-liposomes in artificial cells

Mimicking the process from secretory vesicles to organelles in eukaryotic cell evolution by clustering enzyme-liposomes in artificial cells

  • J Colloid Interface Sci. 2025 Oct 15:696:137863. doi: 10.1016/j.jcis.2025.137863.
Shushan Mo 1,  Xiaoya Li 2,  Yuanhang Li 2,  Qingqing Leng 2,  Yujing Hu 2,  Jiacong Ai 3,  Junyao Deng 3,  Zhenhua Li 3,  Huifang Liu 4,  Xueyi Wang 5
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Hebei University, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Baoding 071002, China; The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China.
  • 2 College of Pharmaceutical Sciences, Hebei University, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Baoding 071002, China.
  • 3 The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China.
  • 4 College of Pharmaceutical Sciences, Hebei University, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Baoding 071002, China. Electronic address: liuhuifang@hbu.edu.cn.
  • 5 The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China. Electronic address: ixueyi@smu.edu.cn.
PMID: 40378444 DOI: 10.1016/j.jcis.2025.137863
Abstract

Eukaryotic cells exhibit complex multicompartmentalized structures that optimize enzymatic efficiency as a result of continuous evolution. Inspired by this, we developed artificial cell models mimicking the evolutionary process from secretory vesicles to organelles using liquid-liquid phase separation (LLPS). An aqueous two-phase system (ATPS) enabled the creation of membrane-less compartments encapsulating liposomes loaded with glucose oxidase (GOx) and myoglobin (Mb). These liposomes were aggregated using tannic acid (TA) and further coated with metal-phenolic networks (MPN) to mimic organelle formation and abnormal mineralization, respectively. Cascade enzymatic reactions demonstrated that clustering enzyme-liposomes significantly enhanced efficiency, facilitating substrate channelling and minimizing diffusional loss, supporting the hypothesis that enzymatic optimization drove the evolution of eukaryotic organelles. Conversely, excessive TA and MPN coatings inhibited enzymatic activity, illustrating the detrimental effects of abnormal mineralization. This study offers a novel perspective on cellular evolution and the fundamental principles of life.

Keywords

Artificial cells; Artificial organelles; Liquid–liquid phase separation.

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