Opsin‐Free Activation of Bmp Receptors by a Femtosecond Laser
Opsin‐Free Activation of Bmp Receptors by a Femtosecond Laser
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DOI：
10.1002/advs.202308072
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发表时间：
2024-01
期刊：
影响因子：
15.1
通讯作者：
Manjun Xu;Haipeng Wang;Xiaoying Tian;Bingyi Li;Shaoyang Wang;Xiao-Yu Zhao;Hao He
中科院分区：
文献类型：
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作者：
Manjun Xu;Haipeng Wang;Xiaoying Tian;Bingyi Li;Shaoyang Wang;Xiao-Yu Zhao;Hao He
骨形态发生蛋白(BMP)信号在分化、器官发生和各种细胞过程中起着至关重要的作用。作为转化生长因子-β超家族的一员，骨形态发生蛋白的启动通常伴随着其他信号通路的串扰，并同时激活其中一些信号通路。单独启动一条单独的途径是相当具有挑战性的。在这项研究中，报道了一种无视素的光学方法，通过在近红外范围内一次扫描紧聚焦的飞秒激光来特异性地激活BMP受体(BMPR)和随后的pSmad1/5/8级联。通过瞬时双光子激发细胞膜附近的固有局部黄素，光激活驱动预先形成的BMPR复合体的构象变化，使它们能够通过BMPR-II与BMPR-I中的GS结构域结合和磷酸化。这种方法启动了pSmad1/5/8信号，而p38和pSmad2很少被干扰。在显微系统的基础上，原代脂肪干细胞在420×420微米的面积内被单次激光扫描1.5 S光激活，21d后显示pSmad1/5/8上调和成骨细胞分化。因此，报道了一种无视素、特异性和非侵入性的光学方法来启动BMP信号，该方法很容易由双光子显微镜系统实现。
Bone morphogenetic protein (BMP) signaling plays a vital role in differentiation, organogenesis, and various cell processes. As a member of TGF‐β superfamily, the BMP initiation usually accompanies crosstalk with other signaling pathways and simultaneously activates some of them. It is quite challenging to solely initiate an individual pathway. In this study, an opsin‐free optical method to specifically activate BMP receptors (BMPR) and subsequent pSmad1/5/8 cascades by a single‐time scan of a tightly‐focused femtosecond laser in the near infrared range is reported. Via transient two‐photon excitation to intrinsic local flavins near the cell membrane, the photoactivation drives conformational changes of preformed BMPR complexes to enable their bonding and phosphorylation of the GS domain in BMPR‐I by BMPR‐II. The pSmad1/5/8 signaling is initiated by this method, while p38 and pSmad2 are rarely perturbed. Based on a microscopic system, primary adipose‐derived stem cells in an area of 420 × 420 µm2 are photoactivated by a single‐time laser scanning for 1.5 s and exhibit pSmad1/5/8 upregulation and osteoblastic differentiation after 21 days. Hence, an opsin‐free, specific, and noninvasive optical method to initiate BMP signaling, easily accomplished by a two‐photon microscope system is reported.