Platelets’ Nanomechanics and Morphology in Neurodegenerative Pathologies

Abstract

The imaging and force–distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs—Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets’ functions. Importantly, the platelets’ signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools.

Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

“…Along with the cell shape, spreading area, and volume, membrane roughness and stiffness were also found useful for differentiation between healthy persons and patients with acute myocardial infarction [ 255 ], type 2 diabetes mellitus (emorheological and atomic force microscopy studies on the experimental clot formations in patients with type 2 diabetes mellitus), hypertension [ 256 ], transient ischemic attacks [ 257 ], and inherited thrombophilia [ 258 ]. We also reported that the PLT membranes in NDDs were significantly stiffer than the control PLTs ( Figure 2 D, [ 254 ]). The greatest membrane rigidification was observed in ALS PLTs and corresponded well with their highest activation and aggregation stages among all NDDs ( Figure 2 D and Figure 5 ).…”

“…The process and degree of PLT activation are formally divided into four stages [ 150 ]. While the adhered PLTs from healthy individuals appear in a resting or poorly activated state, in PD they are in an activation stage II or III, in ALS they are in the most advanced stages III and IV ( Figure 5 , [ 254 ]), and finally in AD the PLTs exhibit an activation state II [ 254 ].…”

Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies

“…It is to be noted that our recent studies exploring imaging and force-distance curve modes of atomic force microscopy revealed strong and specific changes in the morphometric and mechanical parameters of the peripheral blood cells, platelets, and erythrocytes [12,13] in NDD pathologies. Lower membrane surface roughness, area, and height and significantly higher stiffness; different degrees of activation; distinct pseudopodia; and nanocluster formation were common features of platelets from patients with NDDs; the alterations were less pronounced in PD than in ALS [12].…”

“…It is to be noted that our recent studies exploring imaging and force-distance curve modes of atomic force microscopy revealed strong and specific changes in the morphometric and mechanical parameters of the peripheral blood cells, platelets, and erythrocytes [12,13] in NDD pathologies. Lower membrane surface roughness, area, and height and significantly higher stiffness; different degrees of activation; distinct pseudopodia; and nanocluster formation were common features of platelets from patients with NDDs; the alterations were less pronounced in PD than in ALS [12]. We proved common modification of the surface nanostructure and of morphometric and nanomechanical features of erythrocytes in the studied NDDs relative to healthy cells, as well as aging-induced transformation that followed different aging pathways for NDDs and normal healthy states [13].…”

“…A plethora of investigations have been performed to identify biomarkers-biochemical, imaging, and genetic [4][5][6][7]. In recent years, different biofluids, including cerebrospinal fluid (CSF) and blood, as well as peripheral blood cells were extensively screened for NDDs' biomarkers [8][9][10][11][12][13][14].…”