Massive Solubility Changes in Neuronal Proteins upon Simulated Traumatic Brain Injury Reveal the Role of Shockwaves in Irreversible Damage.
Amir Ata SaeiHassan GharibiHezheng LyuBrady NilssonMaryam JafariHans Von HolstRoman A ZubarevPublished in: Molecules (Basel, Switzerland) (2023)
We investigated the immediate molecular consequences of traumatic brain injuries (TBIs) using a novel proteomics approach. We simulated TBIs using an innovative laboratory apparatus that employed a 5.1 kg dummy head that held neuronal cells and generated a ≤4000 g-force acceleration upon impact. A Proteome Integral Solubility Alteration (PISA) assay was then employed to monitor protein solubility changes in a system-wide manner. Dynamic impacts led to both a reduction in neuron viability and massive solubility changes in the proteome. The affected proteins mapped not only to the expected pathways, such as those of cell adhesion, collagen, and laminin structures, as well as the response to stress, but also to other dense protein networks, such as immune response, complement, and coagulation cascades. The cellular effects were found to be mainly due to the shockwave rather than the g-force acceleration. Soft materials could reduce the impact's severity only until they were fully compressed. This study shows a way of developing a proteome-based meter for measuring irreversible shockwave-induced cell damage and provides a resource for identifying protein biomarkers of TBIs and potential drug targets for the development of products aimed at primary prevention and intervention.
Keyphrases
- traumatic brain injury
- immune response
- cell adhesion
- oxidative stress
- protein protein
- single molecule
- single cell
- randomized controlled trial
- induced apoptosis
- binding protein
- spinal cord injury
- amino acid
- cerebral ischemia
- stem cells
- high resolution
- resting state
- gene expression
- high throughput
- white matter
- dna methylation
- cell proliferation
- molecularly imprinted
- atomic force microscopy
- inflammatory response
- functional connectivity
- cell cycle arrest
- simultaneous determination
- tandem mass spectrometry
- wound healing