Supplementary Figures

Supplementary Figure 1.Self-assembly of CdTe NP/CytC Scanning electron microscopy (SEM) images of SPs with 1:1 CdTe NP/CytC ratio after 72hr of assembly. Scale bars are 10 µm, 3 µm, and 500 nm in (a-c), respectively.

Supplementary Figure 2- Effect of different ratio of CdTe NP/CytC on the formation of SPs SEM image of assembly of SPs with 1:2 CdTe/CytC ratio after 72hr of assembly. Scale bar is 1 µm.

Supplementary Figure 3. Effect of the dimension of NP on the SP size (a) SEM and (b) TEM images of SPs assembled from 13.5 nm CdTe NPs and CytC under the same conditions as those in Fig. 1 and 2. Notice the difference in size. The uniformity and the shape of the SPs remained unchanged. Scale bars are 5µm (a) and 200 nm (b).

SupptimesNoticemer

plementary s of self-assece wider sizegence of SP

Figure 4. Dembly procee distributionwith an equ

LS curves fess betweenn in the earlyuilibrium dia

for particle n CdTe and y stages (24 ameter.

size distribuCytC (1:1 hr) indicativ

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ve of the gra

ifferent C ratio) dual

Supplementary Figure 5. TEM study of morphological changes in 1:1 CdTe/CytC SPs in the course of the assembly 3 hrs (a), 24 hrs (b), and 72 hrs (c). Gradual growth of SPs in size is accompanied by narrowing the size distribution. As such, the size distribution of SPs after 24 h of assembly in (b) is visually wider than the particle size distribution after 72h of assembly in (c). This was indicative of preferred SP diameter corresponding to an equilibrium state. Scale bars are 50 nm (a), 500 nm (b), and 1 µm (c).

Supplementary Figure 6. High resolution (HR) TEM study (a) An additional TEM image of individual CdTe/CytC SP. (b) HR-TEM image of individual NP inside an SP in (a) demonstrating lattice spacing of 0.38 nm that corresponds to (111) zinc blende CdTe. Scale bars are 20 nm (a), and 2 nm (b).

Supplementary Figure 7. Characterization of CytC and its assemblies with CdTe NPs (a) UV-Vis spectra of CytC (red, 5 µM) and SPs (blue, 1:1 CdTe/CytC, 72 hrs). (b) UV-Vis spectrum of freely dispersed CdTe NPs. (c) Control experiment: UV-Vis spectrum of a mixture of Cd(ClO4)2 and CytC under the same conditions as in (a). The spectrum of CytC in presence of Cd(2+) is identical to that without it. (d) CD spectra for free CytC (red, 6 µM), CdTe NPs (black, 6 µM), SPs (blue, 1:1 CdTe/CytC, 72 hrs).

Supplementary Figure 8. FT-IR spectra of CytC (blue), CdTe NPs (green), and CdTe/CytC (red) assembly FTIR spectra obtained after 1 (a), 12 (b), 24 (c), and 72 (d) hrs of assembly. No shifts in the peaks have been observed. Peaks assignment: 3300 cm-1 (N-H bond), 2900 cm-1 (O-H bond), 1700 and 1580cm-1 (C=O bond), 1250 cm-1 (C-N bond), 1200 cm-1 (CH3).

Supplementary Figure 9. Control experiments for attribution of peaks in CD spectra (a) CD spectra for different concentrations of SPs: 6 (blue), 3 (green), and 1.5 (orange) µM based on CdTe NPs. No change in the peak positions was observed, only the intensity of the peaks changed. This observation indicated that, indeed, the CD peaks being discussed were associated with SPs and not some other agglomerated states of CytC or NPs. (b) CD spectra for different components of SP dispersion: redispersed SPs separated from the original supernatant by centrifugation (blue), supernatant with SP removed (orange), and original CytC (red, 6 µM). The CD spectrum of CdTe NP did not have any CD bands in this spectral window (Fig. 2e in the main text, black). The identity of the CD peaks of separated and re-dispersed SPs with those discussed in Fig. 2e (72 h, blue, main text) confirmed the attribution of the CD peaks to SPs and not to potential specific selection of chiral NPs from the solution by interaction with the protein.

SuppCdTe

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Supplementary Figure 12. Time profile of the simulated self-assembly of SPs (a)

Snapshot of a 1:1 mixture consisting of N = 2000 NP and CytC units after

2000equilibration at number density of = N/V = 0.125-3. (b) System potential energy

per unit upon compression from 0.001-3 to 0.125-3 followed by equilibration at 0.125-

3. (c) Dependence of the number of structural units per SP, (MSP), and (d) average

asphericity parameter (AS) of the SPs on the time of the assembly. Error bars in (c) are

obtained from averaging over the SPs assembled in the system at the given time. The

asphericity parameter AS characterizes the shape of the SP: AS = 0 corresponds to a

perfectly spherical shape, AS = 1 corresponds to an infinitely long cylinder55.

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Supplementary Figure 15. Co-assembly of 1:1 CdTe/CytC SPs and NRed into multicomponent SPs (ab) Electrokinetic ζ-potential and the DLS diameters of original NP-CytC SPs (blue) and SPs in presence of NADPH (red) and SP-NRed in presence of NADPH (green). (c-e) TEM images of NP-CytC SPs, SPs in presence of NADPH, and SP-NRed in presence of NADPH. All scale bars are 100 nm. (f-g) UV-Vis and CD spectra of SPs (blue), SPs in presence of NADPH (green), and SP-NRed in presence of NADPH (orange). (h) EDX spectrum of SPs in presence of NADPH in (d) showing the presence of phosphorous indicating SP-bound NADPH.

SupppreseCdTe

plementary ence of NADe/CytC SPs w

Figure 16 SDPH No chawas observed

Scanning eleange in sphed. Scale bar

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Red in presennce of

Supplementary Figure 18. A standard plot of the different concentrations of NO2-

Errors bars indicate the std values from multiple experiments.

Supplementary Notes

Supplementary Note 1

Terminal assemblies are different from their individual components in terms of topology

and dynamics. They were often found in viruses and membranes of biological

molecules1-5.

Supplementary Note 2

The key biological function of CytC is to facilitate the electron transfer process in

photosynthesis via redox reaction of the heme group (Fe+2/Fe+3) present in the core of the

organic protein6-10.

Supplementary Note 3

Previous studues of assemblies of NP and biomacromolecules always relied on

attraction of opposite charges. Typical examples of such assemblies are given in

References 6,11-16.

Supplementary Note 4

Absorbance peaks in the visible part of the spectrum of CytC in both Fe3+ and

Fe2+ forms are associated with electronic π-π*  transitions of the Fe-porphyrin complex17

that is also known as the heme group or simply ‘heme’. The spectrum of Fe+3-CytC

shows the two primary peaks at 409 and 520 nm (Supplementary Fig. 7a, red). Previous

studies showed that the transition of Fe+3-CytC into Fe+2-CytC caused the red-shift of the

strongest Soret-band (λ~410 nm) and the emergence of new β- and α-bands with λ~500

and 550 nm, respectively. The latter two are often called Q-bands18-20.

In our case the reduction of Fe+3-CytC into Fe+2-CytC occurs (Supplementary Fig. 7a).

There is most-likely co-existence of both Fe+3 and Fe+2 forms of CytC all the time18. The

reduction is associated primarily with the transfer of electrons from CdTe core to CytC.

2-(diethyamino)ethanethiol (DMAET) ligands on the NPs surface can also serve as

reducing agents as well18.

From the extinction coefficient21 and absorbance of Fe+3- and Fe+2-CytC at 550 nm we

can estimate the extent of heme reduction. Extinction coefficients (ε) of Fe+3- and Fe+2 -

CytC at 550 nm are 8.4 and 28.0 mM-1 cm-1, respectively. The absorbance at 550 nm of

CytC (ACytC ~ 0.25) and a mixture of CdTe/CytC at 72 hrs (ACdTe/CytC ~ 0.18) was

compared. From Beer-Lambert’s law

A = εbc, (1)

where b is the light path-length and c is the concentration of the chromophore, we

obtained [Fe+3-CytC] and [Fe+2-CytC] as ca. 8.3 and 6.4 µM, respectively. This indicates

~77 % degree of reduction.

Supplementary Note 5

Spectroscopic signatures of denaturation/unfolding of CytC are given in

Supplementary Ref. 22. The destruction of the tertiary structure of this protein is

observed as drastic change of UV-vis spectra of the heme: a blue shift of the Soret band

and disappearance of the peaks in 500-600 nm region, which is obviously not true for

CytC in SPs (Supplementary Fig. 7a).

It is also instructive to evaluate the CD and UV data upon assembly of CytC with

other proteins, such as GroEL22 and cytochrome C oxidase23. One can see clear parallels

in the change of CytC conformation for assembly with CdTe NPs and these proteins.

Comparison of experimental CD spectra of proteins with those in literature20,24 and other

species needs to be made paying attention to the sign conventions for CD peaks. Some

models of CD spectrometers reported CD signals as subtraction of the absorption

intensity of the left-polarized light from right-polarized light while some reported the

opposite.

Upon assembly, the UV-vis edge of CdTe NPs located at 490 nm in freely

dispersed particles undergoes a blue shift to 470 nm due to a change of dielectric

environment around the NPs (Supplementary Fig. 7a,b)25 when transition from water to

CytC surroundings. 

Cd+2 ions did not cause any structural or electronic changes in Fe+3-CytC at the

mixing of 1:1 molar ratio (Supplementary Fig. 7c).

Supplementary Note 6

In addition to NADPH, CytC can scavenge holes due to the presence of

oxidizable amino acid residues, e.g. tyrosine and tryptophan26.

Ri

R Ri j B ij

(t) = 0

(r), (t') = 6 k T (t - t')

F

F F

Supplementary Discussion

Simulation models and methods

Molecular dynamics with a Langevin thermostat was employed to simulate a model

system of DMAET-CdTe NPs and CytC proteins at constant temperature and volume.

Each constituent – NP or a protein molecule - is subject to conservative, random and drag

forces FiC, Fi

R and FiD, respectively. They can be essentially described as solid ‘beads’

whose motion is governed by the Langevin equation:

(2)

Here mi and ri are the bead (unit) mass and position, respectively. The conservative force

FiC is determined by the gradient of the pairwise potentials between a bead and its

neighbors. The random and drag forces represent the bombarding effects of solvent

molecules on a bead. The random force FiR is independent of the conservative force and

satisfies the dissipation fluctuation theorem:

The drag force is related to the bead velocity FiD = -vi, where is the friction coefficient

and vi is the bead velocity. We choose the friction coefficient = 1.0 to limit the ballistic

motion of a bead in a time step to approximately 1.0. The combination of the random

and drag forces serves as a non-momentum-conserving thermostat for the system and

helps to minimize numerical round-off errors that can accumulate during long simulation

runs. Since the steady-state solution of the Langevin equation yields the Boltzmann

velocity distribution, the equilibrated system is in the canonical ensemble, i.e. constant

temperature and volume.

We developed two coarse-grained models to better understand 1) how the NP-

CytC interaction prevents the DMAET-CdTe NPs from assembling into sheets, and 2)

how the renormalized inter-SP charge-charge repulsion between NPs and CytC proteins

during aggregation, as suggested by the potential (Fig. 4b), lead to the self-limiting

assembly of SPs.

.. C R Di i i i im = + + r F F F

(3)

(4)

For the first model, we start with the model CdTe NPs previously used in the

work of Zhang et al.27. The NPs were modeled as 59 beads of diameter 1.0 arranged

into a truncated tetrahedron shape (Supplementary Fig. 11a). The net positive charge (q ~

+3e) is located at the NP center of mass and the dipole vector ( ~ 100D) points from the

center of mass to the bottom face (blue arrow, Supplementary Fig. 11a). Meanwhile,

CytC are modeled as spherical beads with a diameter of dCytC = 4.0. CytC units carry a

charge of q ~ +3e and a dipole moment of ~ 340D. In our simulations, we specify the

charge and dipole moment values in the corresponding reduced units defined as q* =

q/(40)1/2 and * = /(403)1/2, respectively, where 0 is the vacuum permittivity

and is the Lennard-Jones well depth (see below).

The Lennard-Jones 12-6 potential is used to model the face-to-face attraction

between two NPs, i.e. between the constituent beads on the faces (yellow), and the

interaction between NPs and CytC units. The LJ 12-6 interaction is truncated and shifted

to zero at a distance of 2.5. For the interaction between the NP and CytC units, the

center-to-center distance is shifted by an amount = (dbead + dCytC)/2 - dbead = 1.5. The

Lennard-Jones energy well depths, between NP-NP and between NP-CytC are varied

from 0.01kBT to 0.8kBT to probe the conditions at which the NPs alone would assemble

into sheets and those at which the NPs mix with CytC within the SPs. The other pairs

(yellow-white and white-white) interact via the Weeks-Chandler-Andersen potential to

mimic excluded volume (steric) interactions. The screened charge-charge, charge-dipole

and dipole charge interactions between the NPs are localized to the NP centers of mass

and are truncated at a distance of 5.

The rotational degrees of freedom of tetrahedral NPs are incorporated using the

equations for rotation of rigid bodies with quaternions28. We employ the velocity Verlet

scheme to integrate the equation of motion with a time step t = 0.005. The natural units

for these systems are the diameter of a bead, , the mass of a bead, m, and the Lennard-

Jones well depth, a. The time scale is defined as = (ma)-1/2 and the dimensionless

temperature is T* = kBT/a. The number density is defined as = N/V, where N is the total

number of particles and V is the box volume. The NPs and CytC are initialized randomly

in the box and equilibrated under athermal conditions, i.e. all interactions are purely

repulsive. After the mixing stage, the attraction between NPs and CytC is turned on and

the simulation box is gradually compressed to 3 = 0.2-0.3 to facilitate aggregation. The

simulations were performed using HOOMD-Blue29, and an in-house code, which can be

obtained by contacting the authors.

Using the first level coarse-grained model, we indeed observe that in the absence

of CytC the truncated tetrahedral NPs assemble into a sheet (Supplementary Fig. 11b),

reminiscent of that reported in our previous work27,30. However, when mixed with CytC

with a 1:1 molar ratio, the NPs and CytC form spherical aggregates (Supplementary Fig.

11c) when the NP-CytC attraction, aNP-CytC, is comparable to the NP-NP attraction, aNP-

NP.

These results suggest that the sufficiently strong attraction between CytC proteins

and CdTe NPs prevents the NPs from assembling into sheets and leads to the formation

of bionic clusters.

We proceed with developing another model to focus on the self-limiting assembly

of the NPs and CytC proteins based on the observation that the NP shape and dipole

moments are likely of little relevance to the process, as mentioned in the text. In the

second-level coarse-grained model, the DMAET-CdTe NPs and CytC are modeled as

spherical beads with diameters of 1.0 and 1.1, respectively. The size ratio between the

CytC and NPs is chosen to be smaller than in experiment to take into account the flexible

nature of the proteins at room temperature. Similar to the previous model, the NPs and

CytC units interact via the Lennard-Jones 12-6 potential, screened charge-charge

interaction, and dipole-dipole and charge-dipole interactions.

Based on the conditions found from the first-level coarse-grained level, the

Lennard-Jones attraction strength between NPs is chosen as aNP-NP = 4.0kBT and between

CytC aCytC-CytC = 1.0kBT to capture the fact that the NPs spontaneously aggregate at low

concentration and that CytC do not aggregate in the absence of the NPs as their attraction

is insufficient to overcome thermal fluctuations. We varied the NP-CytC attraction

strength aNP-CytC from 1.0kBT to 5.0kBT and observe that for 1.0kBT < aNP-CytC < NP-NP =

4.0kBT the emerging SPs are composed of NPs packing in the core and CytC covering

outside (data not shown).

The screened charge-charge interaction between the NPs and CytC units is

modeled by using the Yukawa potential:

UYukawa(rij) = Aijexp(-rij)/(rij/) (5)

where rij is the distance between two units, Aij and are the repulsion strength and

inverse screening length, respectively. The repulsion strength between freely floating NPs

and CytC is chosen as Aij = 1.0kBT/ and the inverse screening length is chosen as =

1.0 -1, comparable with the diameter of the NPs and CytC units, as estimated in the

previous section.

During the course of the simulation, the NPs and CytC are clustered into SPs

based on their relative distances. A cutoff distance of 1.4 is used to determine if two

units (NPs or CytC) belong to the same SP. Unlike in previous studies, here we treat the

repulsion strength between units in the same SP identically regardless of whether they are

in the core or in the shell of the SP because we do not attempt to characterize the local

density of the NPs and CytC in the shell and the core of individual SPs. Similar to the

model in our previous study31, the repulsion strength between an NP (or a CytC) in an SP

and either a NP or CytC external to the SP, Ainter, is linearly scaled by the SP volume to

model the charge accumulation in the growing counter-ion layers covering the SPs32-35.

Specifically, for units from different SPs, the repulsion strength Ainter is renormalized

with the SP sizes:

Ainter = Aij + (Vi + Vj – V(1)) s, (6)

where Aij = 1.0kBT is the repulsion strength between two freely floating units, chosen as

the baseline; Vi and Vj are the size of the SPs to which the interacting units belong; V(1) =

3/6 is the volume of a single-unit SP; and the slope s is an input parameter representing

how rapidly the repulsion strength increases with the SP sizes. Essentially, s is the first

derivative of Ainter with respect to the SP sizes, and can be related to the slope of the ξ-

potential during the early stage of assembly (Fig. 2f). To first order, s = (Amax – Aij) /

(Vmax– V(1)) where Vmax is the terminal size of the SPs. The maximum value of the inter-

SP repulsion strength, Amax, is determined such that no NP-CytC aggregation occurs at a

given value of NP-CytC. Physically, Amax corresponds to the plateau region of the

electrokinetic potential(Fig. 4b) when the SPs already acquire the terminal size.

Specifically, for NP-CytC = 5.0kBT, we found Amax approximately 5.0kBT/. Because the

number of units per SP is on the order of 104, as estimated above, we do not attempt to

match this number in our simulation mostly due to computational constraints. Instead, we

vary s from 0.001kBT/V(1) to 0.1kBT/V(1) so that the SP terminal size would be in the

range of 30-200 units. As shown in our previous study31 a smaller value of s would give a

larger number of units per SP because that means Ainter reaches Amax at a higher value of

Vmax. The dependence of the SP terminal size on the parameter s will be addressed in a

subsequent study.

It is also important to note that because the inter-SP repulsion is due to the

coexistence of the NPs and CytC it is expected that s is dependent upon the molar ratio of

the mixture; specifically, s decreases with the volume fraction of the CytC because the SP

size increase to infinity when the NPs dominate. In our model, we assume for simplicity

that s is inversely proportional to the NP/CytC molar ratio.

Using the second-level coarse-grained model with the renormalized inter-SP

repulsion, we have observed the formation of uniform-sized SPs from binary mixtures of

NPs and CytC with a 1:1 molar ratio. The system potential energy converges within

statistical error and the SP average size fluctuates around the same value from 5-10

independent runs with different number of NPs and CytC (N = 2000-20000), different

random seeds and different concentrations. Supplementary Fig.12 illustrates an example

of the evolution of the number of units per SP and the SP asphericity parameter in one of

the runs with a 1:1 mixture of 1000 NPs and 1000 CytC units. The results suggest that the

system of uniform-sized SPs is stable and they become more spherical during the

assembly. Supplementary Fig.13 shows example snapshots for different average number

of units per SP (MSP) and number densities.

Supplementary Fig.14 shows an example of the time evolution of the system

potential energy and average number of units per SP where the NP-CytC repulsion

strength is not renormalized. In this case, the assembly is not limited and the SPs are not

uniform in size.

Supplementary Methods

Definition of dimensionless inverse screening length (*) and SP diameter (D*) (Fig.

3f)

To compare qualitatively simulation and experimental data (Fig. 4h), we fit the data sets

with the decay laws f(x) = A exp[-(x-B)/C] + D, where A, B, C and D are fitting

parameters; x is either the NaCl concentration in experiment or the inverse screening

length in simulation.

The obtained parameters are then used to rescale the data points accordingly. For instance,

for the experimental curve (Fig. 2e), given the obtained parameter set of (A1, B1, C1, and

D1) the NaCl concentrations are rescaled as ([NaCl] – B1)/C1. Likewise, the inverse

screening lengths are rescaled as ()/C2. We use the same notation * for the x axis

of the plot in Fig. 4h because the inverse screening length increases monotonously with

the NaCl concentration in the conditions under investigation.

The y axis of the plot in Fig. 4h is obtained by rescaling the SP diameters by (DSP - D)/A.

We use D* to denote the dimensionless SP diameters in both experiment and simulation.

Theoretical calculations of the E-DLVO pair potential between CdTe NPs and CytC

With clear understanding of the tremendous limitations of DLVO theory when it is

applied to nanoscale particles, we decided to test its applicability for the case of CytC and

CdTe NPs. This theory could be useful here in order to obtain a direct evaluation of the

interactions of CdTe NPs with CytC in analytical form and matching it with experimental

studies. It can also be useful in the view of further improvements of DLVO or

alternative theories to nanoscale objects.

The extended DLVO interaction energies between quantum dots are approximated by the

following expression: = + + + + (7),

where VDisp, VDL, VDP, VQ-DP, VHB are London dispersion interactions (Disp), double

layer electrical repulsion (DL), permanent dipole-permanent dipole (DP), charge-dipole

(Q-DP), and hydrophobic (HB) interaction potentials, respectively.

Van der Waals Interaction Potential

The classical definition of van der Waals forces encompasses permanent dipole-

permanent dipole (Keesom), permanent dipole-induced dipole (Debye) and instantaneous

induced dipole-induced dipole (London dispersion) interactions. Quite often in current

literature London dispersion forces are equated with van dew Waals forces due to

relatively small contributions from the Keesom and Debye forces. This is acceptable for

large microscale particles that are often spherical and are uniform in composition.

In case of NPs and proteins a distinction between the van der Waals and the London

dispersion interaction must be taken into account. Both CdTe NPs and CytC have large

permanent dipole moments and therefore both Keesom and Debye interactions are

significant. In fact, we see it would be important to “de-bundle” van der Waals

interactions into three separate contributions, which will be the conceptual framework of

this calculation going forward. Hence we separately calculate the contribution of

permanent dipole-permanent dipole ( ) in the total interaction potential. Note here that

here we implicitly assume additivity of these interactions, which might or might not be

suitable for this system. At this point, we do not have yet an acceptable criterium for

such judgment. The tightness of SP packing leading to the interdependence of the dipolar

moment on the NPs on the slight structural changes,57 and therefore, the ionic

environment around it, gives strong indication of relevance of non-additivity and mutual

interdependence of interactions in such system.

The interparticle potential stemming from the London dispersion forces between CdTe

NPs capped with a shell of DMAET and cytochrome C (CytC) can be evaluated as

follows36,37: = , + , (8)

, where

, = -( A11- A44)( A33- A44)HCdTe-CytC(m,n)12 : m= x+d2RCdTe , n= RCytCRCdTe (9)

V DMAET-CytC= -( A22- A44)( A33- A44)HDMAET-CytC(m,n)12 : m= x2(RCdTe+d) , n= RCytCRCdTe+d (10)

H(m,n), the Hamaker function, is given by

( , ) = + + + + + + + 2 + ++ + +

(11)

Here, is the closest distance between DMAET-capped CdTe NPs and CytC. (11.4 × 10 J)38, (7 × 10 J)39, (9.63 × 10 J)40, (3.72 × 10 J)41

are Hamaker constants for CdTe, hydrocarbons, proteins and water respectively.

(1.9nm) is the radius of CdTe NPs, (0.74nm) is the thickness of the DMAET shell

around the NPs, (1.55nm) is the radius of CytC approximated as a spherical entity.

Double Layer Electrical Repulsion

Double layer repulsive potential between DMAET-capped CdTe NPs and Cyt C can be

evaluated from the following references 42,43:

= 4 ( + ) Γ _ Γ( )

(12)

where

Γ = 8 ∗ tanh( _4 )1 + 1 − 2 ( + ) + 1( ( + ) + 1) tanh ( _4 )

(13)

Γ = 8 ∗ tanh( 4 )1 + 1 − 2 + 1( + 1) tanh ( 4 )

(14)

where is the permittivity of vacuum, is the dielectric constant of water,

is the zeta potential of DMAET-capped CdTe NPs (+26mV), is the

zeta potential of CytC (+7mV). , the reciprocal double layer thickness (Debye length), is

given by,

= ∑ × (15)

where is electric charge (Coloumbs), is Avogadro’s number, and are the

molar concentration and valency of ions, respectively. The Debye length of NaCl

electrolytes specific to ionic strength of interest is calculated accordingly. The practical

Debye length of water is taken to be ≈ 100 nm 44-46.

Dipole-Dipole Interaction Energy

Interaction potential due to two permanent dipoles are derived according to the

interaction model and approximated by the following:

= − 2 ∗ ( + + + )( + 2 + 2 )( + 2 )( + 2 + 2 + 2 )

(16),

where (100D)47,48 and (340D)49 are dipole moment of CdTe NPs and CytC,

respectively.

Charge-Dipole Interaction Energy

Charge-dipole energy according to our interaction model is evaluated from the following:

= − _ − _4 ∗ 1( + + + )

(17)

, where and are the total surface charge of DMAET-capped CdTe

and CytC respectively. We used previously reported surface charge of CdTe NPs (+3e)50.

The surface charge of CytC is obtained from the following relations51:

σ = 2 sinh 2 1 + 1 2cosh ( 4 ) + 1( ) 8ln[cosh( 4 )]sinh ( 2 )

(18) = 4 ∗σ (19)

Hydrophobic Interaction Energy

Hydrophobic interaction is represented by the single exponential function52,

= ( ) (20)

where C is the hydrophobic amplitude and is the decay length. Integrating over x and

substituting in the effective radius, we obtain hydrophobic interaction energy reflective of

our interaction model:

= ( ) ( ) (21)

The strength and the range of hydrophobic interaction were previously shown to depend

on the contact angle of the interacting substrates ( )52. Due to lack of literature data on

the hydrophobicity of DMAET and CytC, we used data based on similar chemical

moieties. The contact angle of DEAET on a gold coated substrate was found to be = 74 53. Furthermore, interfacial reaction of polyimide film with ethanethiol induced

reduction in polarity with water contact angle 64 < < 78 54. A self-assembled

monolayer (SAM) of porphyrin on a gold substrate showed contact angle 76 < <78 34. Based on the contact angle data, we used = −9 (mN/m) and = 2 (nm), which

are based on interacting surfaces with contact angle = 81 52 .

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