A Protein-Based Biosensor for Detecting Calcium by Magnetic Resonance Imaging.
A Protein-Based Biosensor for Detecting Calcium by Magnetic Resonance Imaging.
复制标题
一种基于蛋白质的磁共振钙离子生物传感器。
DOI：
10.1021/acssensors.1c01085
复制
发表时间：
2021-09-24
期刊：
影响因子：
8.9
通讯作者：
Mukherjee, Arnab
中科院分区：
文献类型：
--
作者：
Ozbakir, Harun F.;Miller, Austin D. C.;Fishman, Kiara B.;Martins, Andre F.;Kippin, Tod E.;Mukherjee, Arnab
关键词：
钙响应对比剂的磁共振成像（MRI）提供了一个很有前途的方法，无创性的全脑监测的神经活动在任何任意深度。目前基于MRI的钙探针的例子包括合成分子和纳米颗粒，它们不能用于检查遗传编码形式的钙信号。在这里，我们描述了一种新的MRI钙传感器，完全基于天然存在的钙结合蛋白，称为钙卫蛋白。钙结合导致钙卫蛋白螯合锰离子，从而限制Mn2+增强附近水分子的顺磁弛豫。我们证明，这种机制允许钙卫蛋白改变T1和T2为基础的MRI信号响应生物相关的钙浓度。得到的响应幅度，即，弛豫时间的变化与现有的基于MRI的钙传感器以及其他报道的基于蛋白质的MRI传感器相当。作为其生物学适用性的初步证明，我们使用钙卫蛋白检测溶解的海马细胞制备以及在完整的中国仓鼠卵巢细胞与钙离子载体处理的钙。因此，钙卫蛋白代表了一种有前途的途径，通过结合分子和细胞特异性的遗传编码工具与MRI成像能力，通过散射组织的任何大小和深度的钙信号传导的非侵入性成像。
Calcium-responsive contrast agents for magnetic resonance imaging (MRI) offer a promising approach for noninvasive brain-wide monitoring of neural activity at any arbitrary depth. Current examples of MRI-based calcium probes involve synthetic molecules and nanoparticles, which cannot be used to examine calcium signaling in a genetically encoded form. Here, we describe a new MRI sensor for calcium, based entirely on a naturally occurring calcium-binding protein known as calprotectin. Calcium-binding causes calprotectin to sequester manganese ions, thereby limiting Mn2+ enhanced paramagnetic relaxation of nearby water molecules. We demonstrate that this mechanism allows calprotectin to alter T1 and T2 based MRI signals in response to biologically relevant calcium concentrations. The resulting response amplitude, i.e., change in relaxation time, is comparable to existing MRI-based calcium sensors as well as other reported protein-based MRI sensors. As a preliminary demonstration of its biological applicability, we used calprotectin to detect calcium in a lysed hippocampal cell preparation as well as in intact Chinese hamster ovary cells treated with a calcium ionophore. Calprotectin thus represents a promising path toward noninvasive imaging of calcium signaling by combining the molecular and cellular specificity of genetically encodable tools with the ability of MRI to image through scattering tissue of any size and depth.
登录
查看更多内容
影响因子：
15
作者：
Brophy MB;Nakashige TG;Gaillard A;Nolan EM
通讯作者：
Nolan EM
影响因子：
16.6
作者：
Barandov, Ali;Badelle, Benjamin B.;Jasanoff, Alan
通讯作者：
Jasanoff, Alan
用于多巴胺和血清素的高选择性 p450 磁共振成像传感器的结构引导定向进化。
影响因子：
5.6
作者：
Brustad, Eric M.;Lelyveld, Victor S.;Snow, Christopher D.;Crook, Nathan;Jung, Sang Taek;Martinez, Francisco M.;Scholl, Timothy J.;Jasanoff, Alan;Arnold, Frances H.
通讯作者：
Arnold, Frances H.
影响因子：
6.2
作者：
Garello, Francesca;Vibhute, Sandip;Angelovski, Goran
通讯作者：
Angelovski, Goran
影响因子：
3.3
作者：
Bartelle, Benjamin B.;Szulc, Kamila U.;Turnbull, Daniel H.
通讯作者：
Turnbull, Daniel H.