Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients

Abstract

The availability of biomarkers to evaluate the risk of cardiovascular diseases is limited. High fibrinogen levels have been identified as a relevant cardiovascular risk factor, but the biological mechanisms remain unclear. Increased aggregation of erythrocytes (red blood cells) has been linked to high plasma fibrinogen concentration. Here, we show, using atomic force microscopy, that the interaction between fibrinogen and erythrocytes is modified in chronic heart failure patients. Ischaemic patients showed increased fibrinogen-erythrocyte binding forces compared with non-ischaemic patients. Cell stiffness in both patient groups was also altered. A 12-month follow-up shows that patients with higher fibrinogen-erythrocyte binding forces initially were subsequently hospitalized more frequently. Our results show that atomic force microscopy can be a promising tool to identify patients with increased risk for cardiovascular diseases.

Mechanical Properties of Human Bronchial Epithelial Cells Expressing Wt- and Mutant CFTR

“…In recent years, force microscopy has unveiled the relevance of these nanomechanical properties in important cellular mechanisms, such as migration/locomotion [22], differentiation [23] or as a marker for disease progression [24,25]. It has become evident that these properties are fundamental to explain cell's structure, evolution, and response to different stimuli, making AFM a potential tool for biomedical diagnosis and prognosis, with very promising results already obtained in the areas of cancer [26] or cardiovascular diseases [27].…”

Nanoscale imaging and force probing of biomolecular systems using atomic force microscopy: from single molecules to living cells

“…139 Direct studies about the native conformation and unfolding dynamics of human membrane proteins in the two-dimensional lipid bilayers are still scarce. Practical applications of AFM singlemolecule detection in several diseases have preliminarily demonstrated that the binding force and distribution density extracted from specific molecular interactions can be potential biomarkers capable of discerning disease subtypes 109 and predicting drug efficacies [110][111][112][113] for personalized medicine.…”

“…The stronger fibrinogen-erythrocyte binding in CHF patients can impair blood flow conditions and contribute to the higher thrombosis risk associated with this disease. The 12-month clinical follow-up showed that patients with higher fibrinogen-erythrocyte binding forces at the beginning of the study had a higher probability of being hospitalized due to cardiovascular complications, 109 indicating that fibrinogen-erythrocyte binding forces could effectively indicate the risk of cardiovascular diseases. We have used AFM to investigate the specific drug-target interactions directly on primary lymphoma cells and analyzed the potential links between target properties and practical drug therapeutic outcomes, [110][111][112][113] as shown in Fig.…”

“…108 It is a delight to know that in the recent years researchers have explored probing molecular activities directly on primary cells from clinical patients by using AFM. In 2016, Guedes et al 109 used AFM to investigate molecular interactions directly on the primary erythrocytes prepared from patients with cardiovascular diseases, as shown in Fig. 5(a).…”

Automated Cantilever Exchange and Optical Alignment for High-Throughput Parallel Atomic Force Microscopy

“…The motion of the cantilever is measured using optical beam deflection (OBD), 1 which is converted to a topography measurement of the surface. 2,3 Due to its atomic resolution and the ability to measure mechanical, 4 physical 5 and chemical 6 parameters, AFM has attracted great interest in several industrial applications, such as semiconductor metrology, 7,8 biological and medical applications, 5 material science 9 and data storage. 10 Industrial applications with high-volume manufacturing characteristics require high-throughput, fully automated instruments.…”