posted on 2024-03-11, 16:11authored byYong-Hao Ma, Yan Zhu, Hui Wu, Yao He, Qiang Zhang, Qiuling Huang, Zhimin Wang, Hang Xing, Liping Qiu, Weihong Tan
The cell membrane exhibits a remarkable complexity of
lipids and
proteins that dynamically segregate into distinct domains to coordinate
various cellular functions. The ability to manipulate the partitioning
of specific membrane proteins without involving genetic modification
is essential for decoding various cellular processes but highly challenging.
In this work, by conjugating cholesterols or tocopherols at the three
bottom vertices of the DNA tetrahedron, we develop two sets of nanodevices
for the selective targeting of lipid-order (Lo) and lipid-disorder
(Ld) domains on the live cell membrane. By incorporation of protein-recognition
ligands, such as aptamers or antibodies, through toehold-mediated
strand displacement, these DNA nanodevices enable dynamic translocation
of target proteins between these two domains. We first used PTK7 as
a protein model and demonstrated, for the first time, that the accumulation
of PTK7 to the Lo domains could promote tumor cell migration, while
sequestering it in the Ld domains would inhibit the movement of the
cells. Next, based on their modular nature, these DNA nanodevices
were extended to regulate the process of T cell activation through
manipulating the translocation of CD45 between the Lo and the Ld domains.
Thus, our work is expected to provide deep insight into the study
of membrane structure and molecular interactions within diverse cell
signaling processes.