RESUMEN
In idiopathic scoliotic patients, dynamical intervertebral efforts acting between vertebrae seem to be correlated with the spinal deformity. The quantification of these efforts, which is useful for the orthopedic surgeons to set up their surgical planning is the final objective of the present research. As a first step, we focus in this contribution on the geometrical reconstruction of the spine and especially on the rotation sequences between vertebrae in a multibody approach. The reconstruction process is performed in the standing position with possible bending, using an optimization process based on geometrical data reconstructed from radiographs. The obtained results will serve as input for the subsequent gait motion for which the limited set of geometrical information must be compensated.
Asunto(s)
Disco Intervertebral/fisiopatología , Modelos Biológicos , Movimiento , Rango del Movimiento Articular , Escoliosis/fisiopatología , Columna Vertebral/fisiopatología , Articulación Cigapofisaria/fisiopatología , Simulación por Computador , HumanosRESUMEN
The O-octanoylation of human ghrelin is a natural post-translational modification that enhances its binding to model membranes and could potentially play a central role in ghrelin biological activities. Here, we aimed to clarify the mechanisms that drive ghrelin to the membrane and hence to its receptor that mediates most of its endocrinological effects. As the acylation enhances ghrelin lipophilicity and that ghrelin contains many basic residues, we examined the electrostatic attraction and/or hydrophobic interactions with membranes. Using various liposomes and buffer conditions in binding, zeta potential and isothermal titration calorimetry studies, we found that whereas acylated and unacylated ghrelin were both electrostatically attracted towards the membrane, only acylated ghrelin penetrated into the headgroup and the lipid backbone regions of negatively charged membranes. The O-acylation induced a 120-fold increase in ghrelin local concentration in the membrane. However, acylated ghrelin did not deeply penetrate the membrane nor did it perturb its organisation. Conformational studies by circular dichroism and attenuated total reflection Fourier transformed infrared as well as in silico modelling revealed that both forms of ghrelin mainly adopted the same structure in aqueous, micellar and bilayer environments even though acylated ghrelin structure is slightly more α-helical in a lipid bilayer environment. Altogether our results suggest that membrane acts as a "catalyst" in acylated ghrelin binding to the ghrelin receptor and hence could explain why acylated and unacylated ghrelin are both full agonists of this receptor but in the nanomolar and micromolar range, respectively.