This work used atomic simulations and nanoindentation experiments to investigate hardness, modulus alongside sub-surface crystal defects and dislocation mediated plasticity mechanisms leading to anisotropic pile up and local entropy variation in high entropy alloys. The experimental campaign began from Thermo-Calc phase prediction of Ni25Cu18.75Fe25Co25Al6.25 HEA which followed experimental synthesis of the material using arc melting method and experimental nanoindentation using a Berkovich indenter under load-controlled conditions. Through MD simulations, the value of hf/hmax in monocrystalline HEA was consistently found to be larger than 0.7 which suggested pile-up behaviour to dominate and sink-in behaviour to be unlikely. In the case of (110) and polycrystalline HEA substrates, the elastic work in the indentation hysteresis loop was seen to be larger than the (100) and the (111) orientations which explains that the (110) orientation substrate showed least elastic modulus and hardness while the (111) monocrystalline HEA showed the highest elastic modulus and hardness. From the simulations, a “lasso” type loop on the (110) orientation and cross-over of shear loops on the other orientations accompanied by dislocations of type 1/6 < 112 > (Shockley), 1/2 < 110 > (perfect), 1/3 < 001 > (Hirth), 1/6 < 110 > (Stair rod) and 1/3 < 111 > (Frank partials) were seen to manifest an early avalanche of competing plasticity events. The defects accompanying these dislocations in the sub-surface were identified to be FCC intrinsic stacking faults (ISF), adjacent intrinsic stacking faults (quad faults), coherent ∑3 twin boundary and a coherent twin boundary next to an intrinsic stacking fault (triple fault). The EBSD analysis applied to the MD data showed that the (210) orientation and the< 110 > family of directions were seemed to be preferable to plastically deform the FCC phased Ni25Cu18.75Fe25Co25Al6.25 HEA.
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